Calcium Dysregulation Flashcards
What hormones act to increase serum calcium?
Vitamin D - synthesised in skin/diet intake
Parathyroid hormone - secreted by parathyroid glands
What hormone acts to decrease serum calcium?
Calcitonin - secreted by thyroid parafollicular cells
What would happen to serum calcium levels if parafollicular cells are removed, e.g. in a thyroidectomy?
Although calcitonin can reduce calcium acutely, if you remove the PF cells it’ll have no negative effect
What substance is a good indicator of body Vitamin D levels?
Serum 25-hydroxycholecalciferol
How is vitamin D synthesis regulated?
1,25(OH)2 vitamin D (calcitriol) regulates its own synthesis by decreasing transcription of 1 alpha hydroxylase
Outline the production of calcitriol
- UVB stimulates conversion of 7-dehydrocholesterol into pre-vitamin D3 and pre -vitamin D3 into vitamin D3
- Vitamin D3/Vitamin D2 (from diet) enter the bloodstream and travel to the liver where they undergo hydroxylation reactions catalysed by 25-hydroxylase into 25(OH)cholecalciferol
- 25(OH)cholecalciferol is then hydroxylased further in the kidney to calcitriol by 1-alpha-hydroxylase
What are the effects of calcitriol on the kidneys, gut and bones?
Kidney - increased calcium and phosphate reabsorption
Gut - increased calcium and phosphate absorption
Bones - increased osteoblast activity
What are the effects of PTH on the kidneys, gut and bones?
Kidney - calcium reabsorption, phosphate excretion and increased 1-alpha-hydroxylase activity causing increased calcitriol synthesis
Gut - Indirect effects: increased calcium and phosphate absorption through upregulation of calcitriol synthesis
Bone - calcium resorption
How do PTH and FGF23 regulate serum phosphate levels?
PTH - inhibits sodium-phosphate co-transporter - promotes phosphate excretion via urine
FGF23 - inhibits co-transporter and inhibits calcitriol synthesis
What happens in hypocalcaemia and what are the signs and symptoms?
Sensitises excitable tissues causing muscle cramps, tetany, tingling
Symptoms:
Paraesthesia (hands, mouth, feet , lips)
Convulsions
Arrhythmias
Tetany
Mnemonic - [CATs go numb]
Signs:
Chvosteks’ sign – facial paresthesia
Trousseau’s sign – carpopedal spasm
What sign is being demonstrated in this image?
Chvosteks’ sign - facial paresthesia
What sign is being demonstrated in these image?
Trousseau’s sign – carpopedal spasm
What are the causes of hypocalcaemia?
Low PTH levels = hypoparathyroidism
- Surgical – neck surgery
- Auto-immune
- Magnesium deficiency
- Congenital (agenesis, rare)
Low vitamin D levels
- Deficiency – poor diet/malabsorption, lack of UV light, impaired production (renal failure)
What happens in hypercalcaemia and what are the signs and symptoms?
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)
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 to activate osteoclasts
- Certain cancers (eg squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors
Vitamin D excess (rare)
Outline a cause of primary hyperparathyroidism, its effects and the biochemistry
Parathyroid adenoma producing too much PTH
Calcium increases, but no negative feedback to PTH due to autonomous PTH secretion from parathyroid adenoma
Biochemistry:
High calcium
Low phosphate - increased renal excretion
High PTH - no suppression
How is primary hyperparathyroidism treated?
Parathyroidectomy
What are the risks of untreated hyperparathyroidism?
Osteoporosis
Renal calculi (stones)
Psychological impact of hypercalcaemia – mental function, mood
What is secondary hyperparathyroidism a response to?
Normal physiological response to hypocalcaemia
What biochemistry would you observe in secondary hyperparathyroidism?
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
What are the 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
How is secondary hyperparathyroidism treated?
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 - can’t activate 25 hydroxy vitamin D preparations
- Give Alfacalcidol - 1a hydroxycholecalciferol
What causes tertiary hyperthyroidism and what happens in this condition?
Rare
Occurs in chronic renal failure - can’t make calcitriol
Initially calcium falls, PTH increases (starts as secondary) but over a long period of time PTH continues to increase
Parathyroid glands enlarge (hyperplasia)
Autonomous PTH secretion causes hypercalcaemia
What is the treatment of tertiary hyperparathyroidism?
Parathyroidectomy
What is an important diagnostic tool in hypercalcaemia?
PTH levels
What would you observe in hypercalcaemia due to malignancy?
High calcium
Low/suppressed PTH
If a patient with hypercalcaemia has raised PTH, what is the diagnosis?
Hyperparathyroidism:
- Primary hyperparathyroidism if renal function is normal (eg parathyroid adenoma)
- Tertiary hyperparathyroidism (all 4 glands enlarged – hyperplastic) if chronic renal failure
What would you observe in vitamin D deficiency? (Diagnostic approach)
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 as calcitriol is hard to measure
