Calcium Dysregulation Flashcards
What hormones increase calcium?
Vitamin D:
Synthesised in skin or dietary intake
Aka calcitriol/ 1,25-dihydroxy cholecalciferol
Parathyroid hormone:
Secreted by parathyroid glands
These are the main regulators of calcium and phosphate and act through Kidney, Bone, Gut
Which hormones decrease calcium?
Calcitonin:
Secreted by thyroid parafollicular cells
Can reduce calcium acutely but no pathology if removed
What happens in vitamin D metabolism?
Skin:
UVB sun rays hit skin -
7-dehydrocholesterol -> previtamin D3 -> vitamin D3
Diet:
Ingested vitamin D2 (turned to D3)
Both go into blood
Liver:
25-hydroxylase turns vitamin D3 -> 25-hydroxy cholecalciferol
Kidney:
1 alpha-hydroxylase turns 25(OH)cholecalciferol -> 1,25-dihydroxy cholecalciferol
Basically:
25 hydroxylase in liver
1 alpha hydroxylase in kidney
1,25(OH)2 vitamin D is the active form = calcitriol
How are vitamin D levels in the body measured?
Serum 25 hydroxy cholecalciferol
How is vitamin D synthesis regulated?
1,25 dihydroxy cholecalciferol (calcitriol) regulates its own synthesis
It decreases transcription of 1 alpha hydroxylase
What are the effects of vitamin D on the body?
Bone: Increased osteoblasts (makes bone) activity
Gut:
Increases calcium absorption
Increases phosphate absorption
Kidney:
Increases calcium reabsorption
Increases phosphate reabsorption
So In all increases serum calcium
What are the effects of parathyroid hormone on the body?
Bone:
Increases calcium resorption (calcium taken from bone into blood) (osteoclasts?)
Kidney: Increases calcium reabsorbtion Increases phosphate excretion Increases 1-alpha hydroxylase activity -> This increases vitamin D synthesis
Gut:
Through vitamin D
Increases calcium absorption
Increases phosphate absorption
All increases plasma calcium
The net effect on phosphate is pretty much neutral, equal uptake and excretion
How is serum phosphate regulated?
There is a Na*/PO4 3- cotta spotter in the proximal convoluted tubule of the kidneys
It allows for reabsorbtion of potassium back into the blood
It is inhibited by PTH and FGF23
So these decrease serum phosphate
What is FGF23?
Regulates serum phosphate
Inhibits sodium phosphate co transporter in PCT.
Leads to more phosphate excretion
It also has an inhibitory effect on vitamin D (which itself causes increases phosphate and calcium absorption) so less phosphate is absorbed from gut
Lowers phosphate
What are the symptoms of hypocalcaemia?
Sensitises excitable tissues:
Paraesthesia
Convulsions
Arrhythmias
Tetany (can contract but not relax)
CATs go numb
Chvosteks sign - when facial nerve over zygomatic arch is tapped, eye twiches only in high calcium
Trousseaus sign - inflate blood pressure cuff, hand contracts but cat relax and spasms instead (only in high calcium)
What are the causes of hypocalcaemia?
Low PTH (hypoparathyroidism) : Neck surgery Auto immune Magnesium deficiency (needed for hormone synthesis) Congenital (agenesis, rare)
Low vitamin D:
Deficiency - diet, low UV, malabsorption, impaired production (renal failure)
What are the symptoms of hypercalcaemia?
Renal:
Nephrocalcinosis- kidney stones (made of calcium), cause renal colic
GI effects - anorexia, nausea, constipation, pancreatitis
CNS effects - fatigue, depression, impaired concentration, altered mentation, coma
Stones, abdominal moans, psychic groans
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 that activate osteoclasts
Certain cancers (eg. Squamous cell carcinoma) secrete PTH-related peptide that acts on PTH receptors
Vitamin D excesss
Rare
What is the relationship between parathyroid hormone and calcium levels?
Negative feedback
High calcium, low PTH
Low Calcium, high PTH
Inversely proportional
How does a parathyroid adenoma cause hypercalcaemia?
Primary hyperparathyroidism
Cancer to at least 1/4 parathyroid glands. Produces too much PTH
Calcium increases
Lack of negative feedback (high calcium, PTH should be low). Due to autonomous secretion of PTH from adenoma
Also low phosphate, increased renal excretion
How is primary hyperthyroidism treated?
Caused by a parathyroid adenoma
So surgery - parathyroidectomy
If left untreated:
Osteoporosis
Renal calculi(stones)
Psychological impact
What is secondary hyperparathyroidism?
Can Just be the normal physiological response to hypocalcaemia
PTH is high secondary to low calcium
Also vitamin D deficiency (so PTH does more of the work)
Lack in diet, or UV light. May also be renal failure (can’t make calcitriol)
How is secondary hyperparathyroidism treated?
Vitamin D replacement
(in patients with normal renal function) You give 25 hydroxy vitamin D
Patient coverts it into 1,25 dihydroxy vitamin D via 1 alpha hydroxylase
Ergocalcoferol - 25 hydroxy vitamin D3
Cholecalciferol - 25 hydroxy vitamin D2
In patients with renal failure:
Give alfacalcidol - 1 alpha hydroxycholecalciferol
People with renal failure have inadequate 1 alpha hydroxylation, so can’t activate the other replacements
What is tertiary hyperparathyroidism?
Rare
Chronic renal failure, so chronic vitamin D deficiency
So really low calcium
So much higher PTH to account for this. Parathyroid gland hyperplasia (get much bigger)
This causes hypercalcaemia eventually
Treatment is parathyroidectomy
How is hypercalcaemia diagnosed?
When presented with hypercalcaemia, always look at PTH
If they have raised PTH: hyperparathyroidism (1°/2°/3°)
If renal function is normal - primary hyperparathyroidism (eg. Adenoma)
Tertiary - all 4 glands are enlarged, chronic renal failure
How is vitamin D deficiency diagnosed?
Calcium will be low or low/normal
PTH will be high (secondary hyperparathyroidism) due to low calcium
25(OH) vitamin D is measured (calcitriol is very difficult to measure)
