Calcium Dysregulation Flashcards
What is the key characteristic used to identify tertiary hyperparathyroidism?
Renal failure
What causes secondary hyperparathyroidism?
Vitamin D deficiency
What increases serum calcium?
- vitamin D (skin or diet)
- PTH (parathyroid glands)
via actions on: kidney, bone and gut
What decreases serum calcium?
- calcitonin (thyroid parafollicular cells)
- can reduce calcium acutely, no negative effect if parafollicular cells are removed
What is the active form of vitamin D?
calcitriol/1,25(OH)2cholecalciferol
What is the relationship between 1,25(OH)2 vitamin D (calcitriol) and 1 alpha hydroxylase?
calcitriol regulates it’s own synthesis by decreasing transcription of 1 alpha hydroxylase
What are the effects of calcitriol?
- bones: increased osteoblast activity
- kidney: increased calcium and phosphate reabsorption
- gut: phosphate and calcium absorption
What are the effects of PTH?
- bone: increased calcium resorption from bone
- (increased osteoclast activity)
- kidney: increased calcium reabsorption, increased phosphate excretion and increased calcitriol synthesis.
- gut: the increased calcitriol from the kidney’s effects mean increased calcium and phosphate absorption
Does PTH increase calcium?
yes
What is FGF23?
- hormone which regulates phosphates
- more FGF23, greater phosphate excretion
Where is FGF23 made?
osteocytes
How does FGF23 lower phosphate levels in the body?
- inhibits sodium/phosphate co-transporter, phosphate must be lost to the urine
- inhibits calcitriol formation, therefore less phosphate is reabsorbed.
What is the sodium/phosphate channel inhibited by?
- PTH
- FGF23
What is the effect of hypocalcaemia?
sensitisation of excitable tissues; muscle cramps, tetany and tingling
What are the signs/symptoms of hypocalcaemia?
- paraethesia
- convulsions
- arrhythmias
- tetany
- Chvosteks’ sign
- Trousseau’s sign
What is paraesthesia?
pins and needles in hands, mouth, feet…
What is Chvosteks’ sign?
facial twitching when tapped on cheek
What is trousseau’s sign?
carpopedal spasm
What is tetany?
the ability to contract muscles, but can’t relax them
What are the 2 causes of hypocalcaemia?
- low PTH levels (hypoparathyroidism)
- low vitamin D
What can cause low PTH levels?
- surgery (neck)
- autoimmune issues
- magnesium deficiency
- congenital causes
What can cause low vitamin D levels?
Deficiency
- diet
- lack of UV light
- malabsorption
- impaired production (renal failure)
What are the signs/symptoms of hypercalcaemia?
'stones, abdominal moans and psychic groans' \+ atonal muscles stones: - nephrocalcinosis: kidney stones, renal colic abdominal moans: - anorexia, nausea, dyspepsia, constipation, pancreatitis psychic groans: - fatigue - depression - impaired concentration - coma (>3mmol/L) - altered mentation
What are the possible causes of hypercalcaemia?
- primary hyperparathyroidism
- malignancy
- vitamin D excess (rare)
How does primary hyperparathyroidism cause hypercalcaemia?
- usually: parathyroid gland adenoma
- no negative feeback (high PTH, high calcium)
How can malignancy cause hypercalcaemia?
- bony metastases produce local factors to activate osteoclasts
- certain cancers (eg: squamous cell carcinomas) secrete PTH-related peptide that acts on PTH receptors
What is the relationship between PTH and calcium?
inverse relationship
What are the different types of hyperparathyroidism?
primary, secondary and tertiary hyperparathyroidism
What happens when there is a hyperparathyroid adenoma?
- excess PTH is produced
- calcium increases, no negative feedback due to autonomous PTH secretion from the adenoma
- primary hyperparathyroidism
What is the biochemistry of primary hyperparathyroidism?
- high calcium
- low phosphate
(increased renal phosphate excretion - sodium/phosphate transporter inhibited) - high PTH (not suppressed)
How do you treat primary hyperparathyroidism?
parathyroidectomy (removal of the gland)
What are the effects of untreated hyperparathyroidism?
- osteoporosis
- renal calculi (stones)
- psychological impact
What happens in secondary hyperparathyroidism?
normal physiological response to hypocalcaemia
- low/normal calcium
- normal feedback response
- increased PTH (high secondary to calcium)
What causes secondary hyperparathyroidism?
Vitamin D deficiency commonly: - diet - reduced sunlight rarely: - renal failure (no calcitriol in renal failure)
How do you treat secondary hyperparathyroidism?
Normal kidney function - 25 hydroxy vitamin D - produceds D2 + D3. Renal failure - inadequate-1-alpha hydroxylation, can't activiate it. - alfacalcidol (active vitamin D)
What happens in tertiary hyperparathyroidism?
- chronic renal failure
- chronic vitamin D deficiency
- low vitamin D
(can’t make calcitriol) - over production of PTH (PTH glands hyperplasia)
- causes hypercalcaemia
How do you treat tertiary hyperparathyroidism?
parathyroidectomy
What should be done first when a patient presents with high calcium?
look at PTH
How do you differentiate between primary hyperparathyroidism and hypercalcaemia due to malignancy?
look at PTH levels, high in primary, low in malignancy
What are the key characteristics of tertiary hyperparathyroidism?
- chronic renal failure
- all 4 glands are enlarged (hyperplastic)
How is vitamin D measured?
25 (OH) vitamin D
What is the normal progression of secondary hyperparathyroidism?
- switches to tertiary hyperparathyroidism
- due to constant PTH production from vitamin D deficiency
How is hypercalcaemia of malignancy managed?
Bisphosphonates
- inhbit osteoclasts
- lowers serum calcium and reduces bony pain
