Calcium Dysregulation Flashcards
Which hormones increase serum calcium?
Vitamin D
Parathyroid hormone
Which hormone decreases serum calcium?
Calcitonin
What is the precursor molecule of pre-vitamin d3?
7-dehydrocholesterol
Which enzyme catalyses the conversion of vitamin d3 to 25-hydroxycholecalciferol?
Renal 25-hydroxylase
Which enzyme catalyses the conversion of 25-hydroxycholecaliciferol?
1-alpha hydroxylase
What are the effects of calcitriol?
Increased osteoblast activity
Increased enterocyte calcium absorption (Calbindin-D expression)
Increased serum phosphate absorption
Increased calcium and phosphate reabsorption
What are the effects of PTH?
Increased calcium resorption from bone Increased calcium absorption Increased phosphate absorption Increased calcium reabsorption Increased phosphate excretion Increased 1-alpha-hydroxylase activity
Which transporter is responsible for phosphate renal reabsorption?
NPT2
What effects does PTH have on renal phosphate reabsorption?
Inhibits NPT2 transporter, therefore in hyperparathyroidism , serum phosphate is low due to increased urine phosphate excretion
What effect does FGF-23 have on calcitriol?
Inhibits the synthesis of calcitriol.
Less phosphate reabsorption from gut
What are the clinical features of hypocalcaemia?
Sensitises excitable tissues, muscle cramps, tetany, tingling
Paraesthesia (hands, mouth, feet, lips)
Convulsions
Arrhythmias
Tetany
CATs go numb
Which sign is attributed to twitching of the zygomatic arch in patients with hypocalcaemia?
Chvostek’s sign
What is trousseau’s sign in hypocalcaemia?
Carpopedal spasm
What are the causes of hypocalcaemia?
Low PTH levels = hypoparathyroidism
- Surgical- neck surgery
- Auto-immune
- Magnesium deficiency
- Congenital
Low vitamin D levels
-Deficiency
What are the signs of hypercalcaemia?
Stones- renal effects- nephrocalcinosis (kidney stones and renal colic)
Abdominal moans- GI effects (Anorexia, nausea, dyspepsia, constipation and pancreatitis)
Psychic groans - Fatigue, depression, impaired concentration, altered mentation, coma
What are the causes of hypercalcaemia?
Primary hyperparathyroidism
- Excess production of PTH (parathyroid gland adenoma)
- There is no negative feeadback (elevated production of PTH)
Malignancy (bony metastases, produce local factors to activate osteoclast)
Certain cancer (squamous cell carcinoma), secrete PTH related peptide that acts at PTH receptors
Which cells detect serum calcium in parathyroid gland?
G-coupled calcium sensing receptors on the parathyroid cells.
What is the relationship between PTH and calcium ions?
There is an inverse relationship between calcium concentration and PTH production
What is the main cause of primary hyperparathyroidism?
Parathyroid adenoma –> Elevated production of PTH
Calcium increases, however there is no negative feedback to PTH
What is the biochemistry of hyperparathyroidism?
High calcium
Low phosphate - increased renal phosphate excretion (inhibition of NPT2)
High PTH
What is the main treatment of primary hyperparathyroidism?
Parathyroidectomy
What are the associated risks of untreated hyperparathyroidism?
Osteoporosis
Renal caliculi
Mental function and mood is impaired.
What is serum calcium of secondary hyperparathyroidism?
Low serum calcium, physiological response to hypocalcaemia
What are the common causes of secondary hyperparatyroidism?
Vitamin D deficiency
What is the treatment of secondary hyperparathyroidism?
Vitamin D replacement
25-hydroxy vitamin D
What is the treatment for secondary hyperparathyroidism in patients with renal failure?
Alfacalcidol (inadequate 1-alpha hydroxylation)
What is the common cause of tertiary hyperparathyroidism?
Chronic renal failure
Parathyroid gland hyperplasia- autonomous PTH secretion causes hypercalcaemia.
What is the normal physiological response to hypercalcaemia for PTH?
PTH decreases (suppressed)
What is the surrogate marker to measure inactive Vitamin-D?
25-Hydroxy vitamin D.
