Calcium Dysregulation Flashcards
Hormones that increase calcium and phosphate
Vitamin D - Synthesised in skin or intake via diet
Parathyroid hormone (PTH) (secreted by parathyroid glands)
Main regulators of calcium & phosphate homeostasis via actions on kidney, bone and gut
Hormones that decrease calcium and phosphate
Calcitonin (secreted by thyroid parafollicular cells)
Can reduce calcium acutely, but no negative effect if parafollicular cells are removed eg thyroidectomy
Vitamin D metabolism
Serum 25-OH vitamin D = good indicator of body vitamin D status
1,25(OH)2 vitamin D (calcitriol) - active form of vitamin D - regulates its own synthesis by decreasing transcription of 1 alpha hydroxylase
Vitamin D pathway in body
UVB
7-dehydrocholesterol
Pre vitamin D3
Vitamin D3 - hydroxylated by 25-hydroxylase from liver - 25(OH) vitamin D
Hydroxylated again by 1 alpha hydroxylase from kidney - calcitriol formed
OR
Vitamin D2 from diet that goes through same process as D3
Effects of calcitriol
Increased osteoblast activity in bones
↑ Ca2+ and PO43- reabsorption in kidneys
Increased calcium and phosphate absorption in gut
Net increase in calcium and phosphate
Actions of parathyroid hormone (PTH)
↑ Ca2 resorption from bone
↑ Ca2+ absorption and ↑ PO43- absorption in gut
↑ Ca2+ reabsorption ↑ PO43- excretion (inhibit sodium phosphate cotransporter) ↑ 1-a-hydroxylase activityin kidneys - stimulate calcitriol synthesis - stimulate gut
Increased calcium but normal phosphate
FGF23
Regulate serum phosphate
Inhibit sodium phosphate cotransporter to stop phosphate reabsorption in kidney
Inhibit calcitriol formation
Hypocalcaemia
Sensitises excitable tissues; muscle cramps, tetany, tingling
Signs & symptoms Paraesthesia (hands, mouth, feet , lips) Convulsions Arrhythmias Tetany
Mnemonic - [CATs go numb]
Chvosteks’ sign – facial paresthesia
Trousseau’s sign – carpopedal spasm
Causes of hypocalcaemia
Low PTH levels = hypoparathyroidism Surgical – neck surgery Auto-immune Magnesium deficiency Congenital (agenesis, rare)
Low vitamin D levels
Deficiency – diet, UV light, malabsorption, impaired production (renal failure)
Hypercalcaemia
‘Stones, abdominal moans and psychic groans’
Reduced neuronal excitability – atonal muscles
Stones – renal effects
Nephrocalcinosis – kidney stones, renal colic
Abdominal moans - GI effects
Anorexia, nausea, dyspepsia, constipation, pancreatitis
Psychic groans - CNS effects
Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
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 to activate osteoclasts
Certain cancers (eg squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors
Vitamin D excess (rare)
Relationship between PTH and calcium
Increased PTH - decreased calcium
Decreased PTH - increased calcium
Primary Hyperparathyroidism
Parathyroid adenoma producing too much PTH
Calcium increases, but no negative feedback to PTH due to autonomous PTH secretion from parathyroid adenoma
High calcium
Low phosphate – increased renal phosphate excretion (inhibition of Na+/PO43- transporter in kidney)
High PTH (not suppressed by hypercalcaemia)
Treatment of primary hyperparathyroidism
Parathyroidectomy is treatment of choice for primary hyperparathyroidism
Untreated hyperparathyroidism has risks of
Osteoporosis
Renal calculi (stones)
Psychological impact of hypercalcaemia – mental function, mood
Secondary hyperparathyroidism
Secondary hyperparathyroidism is a normal physiological response to hypocalcaemia
Calcium will be low or low/normal
PTH will be high (hyperparathyroidism) secondary to the low calcium
This is different from primary hyperparathyroidism where calcium is high
Causes of secondary hyperparathyroidism
Most common cause of secondary hyperparathyroidism is vitamin D deficiency
Commonly - diet, reduced sunlight
Less common, but important = renal failure – can’t make calcitriol in renal failure
Treatment of secondary hyperparathyroidism
Vitamin D replacement
In patients with normal renal function
Give 25 hydroxy vitamin D
Patient converts this to 1,25 dihydroxy vitamin D via 1a hydroxylase
Ergocalciferol 25 hydroxy vitamin D2
Cholecalciferol 25 hydroxy vitamin D3
In patients with renal failure - inadequate 1a hydroxylation, so can’t activate 25 hydroxy vitamin D preparations
Give Alfacalcidol - 1a hydroxycholecalciferol
Tertiary hyperparathyroidism
Tertiary hyperparathyroidism = rare
Occurs in chronic renal failure
Can’t make calcitriol
PTH increases (hyperparathyroidism)
Parathyroid glands enlarge (hyperplasia)
Autonomous PTH secretion causes hypercalcaemia
Treatment is parathyroidectomy
Diagnostic approach to hypercalcaemia
When looking at a patient with hypercalcaemia, always look at the PTH!
Normal PTH response to hypercalcaemia is for PTH to fall
Hypercalcaemia due to malignancy
High calcium (hypercalcaemia)
Low/suppressed PTH
If patient with hypercalcaemia has raised PTH, the diagnosis is hyperparathyroidism Primary hyperparathyroidism if renal function is normal (eg parathyroid adenoma) Tertiary hyperparathyroidism (all 4 glands enlarged – hyperplastic) if chronic renal failure
Diagnostic approach to vitamin D deficiency
Calcium will be low or low/normal
PTH will be high (hyperparathyroidism) secondary to the low calcium
Vitamin D is measured as 25 (OH) vitamin D
Calcitriol (1,25 dihydroxy vitamin D) is very difficult to measure
Regulate phosphate
FGF23
