Calcium dysregulation Flashcards
How to increase serum calcium
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
What decreases serum calcium
Calcitonin (secreted by thyroid parafollicular cells)
Can reduce calcium acutely, but no negative effect if parafollicular cells are removed eg thyroidectomy
Explain the metabolism of vitamin D
Synthesis from UV exposure
Or from diet
7-dehydrocholesterol –> vitamin D3 —> In the liver, 25-hydroxylase —> 25 (OH) cholecalciferol —> 1 alpha hydroxylase in kidney –> 1,25 OH cholecalciferol
What do we measure in blood to show vitamin D status
25 OH cholecalciferol
How is vitamin D (calcitriol) regulated?
Via decreasing transcription of 1 alpha hydroxylase
What are the effects of calcitriol?
Increase osteoblast activity in bones
Increase in Ca2+ and PO43- reabsorption in kidney
Increase in Ca2+ and PO43- reabsorption in gut
What are the actions of parathyroid hormone?
Ca2+ resorption from bone
Increase in Ca2+ and PO43- excretion and 1 alpha hydroxylase activity (leads to more calcitriol) in kidney
—This leads to increase in Ca2+ and PO43- reabsorption in gut
Net result of PTH and Vitamin D is increase in plasma calcium
How does PTH result in excretion of PO43- from kidney?
Phosphate reabsorption occurs via the gut and the kidneys. Phosphate is reabsorbed via sodium phosphate transporter cells. In the kidney, shown here, reabsorption of phosphate via these transporters results in less sodium excretion in the urine.
Increased phosphate loss in the urine would lower serum phosphate levels.
PTH inhibits renal phosphate reabsorption by inhibiting these transporters – so in primary hyperparathyroidism, serum phosphate is low due to increased urine phoshate excretion.
FGF23 – derived from bone – also inhibits phosphate reabsorption in the kidneys by inhibiting these transporters and also inhibits synthesis of calcitriol, causing less phosphate absorption from the gut.
What are signs of hypocalcaemia?
Sensitises excitable tissues; muscle cramps, tetany, tingling
Paraesthesia (hands, mouth, feet , lips)
Convulsions
Arrhythmias
Tetany
Mnemonic - [CATs go numb
Sensitises excitable tissues; muscle cramps, tetany, tingling
Signs & symptoms
Paraesthesia (hands, mouth, feet , lips)
Convulsions
Arrhythmias
Tetany
Mnemonic - [CATs go numb
Trousseau’s sign – carpopedal spasm
Chvosteks’ sign – facial paresthesia
What are the causes of hypocalcaemia in terms of hypoparathyroidism?
Low PTH levels
Surgical – neck surgery
Auto-immune
Magnesium deficiency
Congenital (agenesis, rare)
What are the causes of hypocalcaemia in terms of low vitamin D levels?
Deficiency – poor diet/malabsorption, lack of UV light, impaired production (renal failure)
What are the signs and symptoms of hypercalcaemia?
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)
What happens when calcium is high?
Negative feedback - decrease in PTH
What does a parathyroid adenoma do?
Parathyroid adenoma producing too much PTH
Calcium increases, but no negative feedback to PTH due to autonomous PTH secretion from parathyroid adenoma
Primary hyperparathyroidism
What is the biochemistry of primary hyperparathyroidism
High calcium
Low phosphate – increased renal phosphate excretion (inhibition of Na+/PO43- transporter in kidney)
High PTH (not suppressed by hypercalcaemia)
What is the treatment for primary hyperparathyroidism?
Parathyroidectomy is treatment of choice for primary hyperparathyroidism
What are the risks of untreated hyperparathyroidism
Osteoporosis
Renal calculi (stones)
Psychological impact of hypercalcaemia – mental function, mood
What happens in 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
What is the cause 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
What is the treatment for 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
What is tertiary hyperparathyroidism?
Caused by chronic renal failure as you can’t make calcitriol so vitamin D deficiency, therefore reduction in calcium
PTH therefore goes up drastically and the parathyroid glands have hypertrophy
Then an increase in calcium reabsorption
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
What to do when a patient has high calcium
What does normal PTH response show
What does raised PTH show
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
What is the 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
