Calcium Dysregulation Flashcards
What can increase Calcium in the body?
Vitamin D
Parathyroid hormone
What can decrease Calcium in the body?
Calcitonin
Not sure of physiological role
What is Calcitonin secreted by?
Thyroid parafollicular cells
What are the main steps of Vitamin D metabolism
UVB shines on the skin
Converts 7-dehydrocholesterol to Pre-Vitamin D3
Converts to Vitamin D3
In the liver 25-hydroxylase converts it to 25(OH)cholecalciferol
In the Kidney 1-alpha-hydroxylase converts to 1,25(OH)2 cholecalciferol
What is the active form of Vitamin D?
1,25(OH)2 cholecalciferol
aka Calcitriol
Cannot be measured
What do you measure for Vitamin D?
Good marker for how much Vitamin D someone has
25(OH)cholecalciferol
What does effect does Calcitriol have on 1-alpha hydroxylase?
Negative feedback
What are the effects of Calcitriol?
Absorb phosphates and calcium in the gut
Increased osteoblast activity
What are the effects of PTH?
Increased calcium and phosphate reabsorption in the gut by increasing the synthesis of Calcitriol
(Increases 1-alpha hydroxylase activity)
Increases reabsorption of calcium and excretion of phosphate in kidney
PTH stimulates osteoclasts to reabsorb calcium from bone
What is the net effect of PTH?
Increases synthesis of Calcitriol
Increase Ca mobilisation from bone
Increases plasma Calcium
How does PTH and FGF23 regulate serum phosphate?
Via sodium/phosphate co-transporter
PTH inhibits this channel
Stops phosphate from being reabsorbed increasing excretion
FGF23 inhibits calcitriol
What is FGF23?
Factor that is important in the regulation in phosphate
Role is to reduce serum phopsphate
- inhibits calcitriol
- inhibits sodium/phosphate co-transporter
What are the signs of Hypocalcaemia?
Paraesthesia
Convulsions
Arrhythmias
Tetany
CATS go numb
What are the two signs that are present with hypocalcaemia?
Chvosteks’ sign
Trousseau’s sign
What causes low PTH levels?
Surgical - neck surgery
Auto-immune
Magnesium deficiency
Congenital (agenesis, rare)
What causes low Vitamin D?
Deficiency - diet, UV light, malabsorption, impaired production (renal failure)
What are the signs of hypercalcaemia?
Stones
Abdominal moans
Psychic groans
What are stones?
Renal effects
Nephrocalcinosis- kidney stones, renal colic
What are abdominal moans?
Anorexia Nausea Dyspepsia Constipation Pancreatitis
What are psychic groans?
CNS effects
Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
What is the cause of hyper calcaemia?
Primary hyperparathyroidism
Malignancy
Vitamin D excess (rare)
What are the features of primary hyperparathyroidism?
Too much PTH
Usually due to a parathyroid gland adenoma
No negative feedback - high PTH, but high calcium
What are the features of malignancy causing hypercalcaemia?
Bony metastases produce local factors to activate osteoclasts Certain cancers (eg squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors
What happens when serum calcium falls?
Feedback to parathyroid gland
Calcium sensor receptor senses this and stimulates PTH production
What happens when serum calcium is high?
Feedback to parathyroid gland
Calcium sensor receptor senses this and inhibits PTH production
What is an adenoma?
benign tumour of a endocrine gland
What would a parathyroid adenoma result in?
Over production of PTH
Increases serum calcium
Tumour does not respond to negative feedback
Primary hyperparathyroidism
What is the biochemistry of primary hyperparathyroidism?
High calcium
Low phosphate - increased renal phosphate excretion (inhibition of Na/Phosphate transporter in kidney)
High PTH
What is the treatment of 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
How does secondary hyperparathyroidism occur?
Calcium is low
Sensed and PTH is stimulated
How are 1ry and 2ry hyperparathyroidism different?
In 1ry calcium is high
What is the most common form of secondary hyperparathyroidism?
Vitamin D deficiency
What causes Vitamin D deficiency?
Commonly- diet, reduced sunlight
Less common cause is renal failure (can’t make 1-alpha hydroxylase)
How do you treat secondary hyperparathyroidism?
Vitamin D replacement
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
How do you treat secondary hyperparathyroidism in those with renal failure?
inadequate 1a hydroxylation, so can’t activate 25 hydroxy vitamin D preparations
Give Alfacalcidol - 1a hydroxycholecalciferol
What causes tertiary hyperparathyroidism?
Chronic kidney disease
Chronic Vitamin D deficiency
Chronic low calcium
Increase in PTH to try and restore Ca to normal
Parathyroid glad become autonomous and overactive
Eventual excess of calcium
How do you treat tertiary hyperparathyroidism?
Parathyroidectomy
Summarise primary hyperparathyroidism?
Parathyroid adenoma, makes too much PTH
Calcium increases, but PTH stays high (no negative feedback)
Summarise secondary hyperparathyroidism?
Normal physiological response to low calcium (commonly caused by low vitamin D)
Calcium low/low-normal, PTH high
Summarise tertiary hyperparathyroidism?
Complication of chronic renal failure and prolonged calcitriol deficiency
Initially calcium falls and PTH rises (secondary hyperparathyroidism), but over a long period high PTH drive by enlarged parathyroid glands increases calcium
How do you diagnose hypercalcaemia?
Always look at the PTH
How will hypercalcaemia caused by malignancy present?
Normal PTH response to hypercalcaemia is for PTH to fall
Hypercalcaemia due to malignancy
High calcium (hypercalcaemia)
Low/suppressed PTH
If PTH is high how do decide which form of hyperparathyroidism it is?
Primary hyperparathyroidism if renal function is normal (eg parathyroid adenoma)
Tertiary hyperparathyroidism (all 4 glands enlarged – hyperplastic) if chronic renal failure
How do you diagnose 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
