Calcium + Phosphate Regulation Flashcards
What is the most important vitamin D metabolite?
1, 25-dihydroxycholecalciferol (calcitriol)
What is the principle effect of calcitriol?
Increase calcium, magnesium + phosphate absorption in the small intestines
What are the other effects of calcitriol?
Increased reabsorption of calcium + decreased reabsorption of phosphate in the kidneys (via FGF23)
Stimulates osteoclast formation from precursors
Stimulates osteoblasts to make osteoclast-activating factors (OAFs e.g. RANKL)
What does vitamin D deficiency cause? State 5 signs/ symptoms.
Lack of bone mineralisation Softening of bone (can lead to bowing of legs) Bone deformities Bone pain Severe proximal myopathy
What are the different names for vitamin D deficiency in children and adults?
Children: Rickets
Adults: Osteomalacia
State 5 causes of vitamin D deficiency.
Malabsorption/ dietary insufficiency Lack of sunlight Liver disease Renal disease Receptor defects
Which step, in vitamin D metabolism, required UV light?
Conversion of 7-dehydrocholesterol in the skin to cholecalciferol (vitamin D3)
Describe the 2 hydroxylation reactions in vitamin D metabolism.
Cholecalciferol hydroxylated to form 25-hydroxycholecalciferol in the Liver
In the kidneys undergoes 2nd hydroxylation (by 1-alpha-hydroxylase) to form 1, 25-dihydroxycholecalciferol (calcitriol)
What can stimulate 1-alpha-hydroxylase in the kidneys?
Parathyroid Hormone (PTH)
How can lack of sunlight cause vitamin D deficiency?
Less 7-dehydrocholesterol is converted to cholecalciferol
How can liver disease cause vitamin D deficiency?
Liver is where the 1st hydroxylation takes place + where 25-hydroxycholecalciferol is stored
How can renal disease cause vitamin D deficiency?
The 2nd hydroxylation step takes place in the kidneys (via 1-alpha-hydroxylase)
What is usually measured to gage the level of calcitriol? Whatcondition must be fulfilled for this to be a good measure of calcitriol?
25-hydroxycholecalciferol
Only a good measure in the case of normal renal function
Describe the diagnostic characteristics of vitamin D deficiency.
Plasma Calcium = LOW
Plasma 25-hydroxycholecalciferol = LOW
Plasma PTH = HIGH (secondary hyperparathyroidism stimulated by the hypocalcaemia)
Plasma Phosphate = LOW
Radiological findings e.g. widened osteoid seams
What would you expect the plasma phosphate level to be in someone with renal failure and why?
HIGH: because the GFR is low + there is a decrease in plasma excretion via the kidneys
What would you expect the plasma calcium level to be in someone with renal failure and why?
LOW: because they are not producing as much calcitriol (due to renal failure interfering with 1-alpha hydroxylase) so there is less Ca2+ absorption in the small intestines
What are the consequences of hypocalcaemia caused by renal failure?
Decrease in bone mineralisation + increase in bone resorption (because of an increase in PTH) leading to osteitis fibrosa cystica
Imbalance in calcium + phosphate can also lead to the formation of salts that can be deposited in extra-skeletal tissue causing extra-skeletal calcification
What can vitamin D excess lead to?
Hypercalcaemia + hypercalciuria (due to increased intestinal absorption of calcium)
What can vitamin D excess result from?
Excessive treatment with active metabolites of vitamin D, as in patients with chronic renal failure
Granulomatous disease: granulomatous tissue has 1-alpha-hydroxylase so it can be a source of ectopic calcitriol
What is the treatment for primary hyperparathyroidism?
Parathyroidectomy
What is the normal plasma calcium range?
2.2-2.6 mmol/L
State 2 hormones that increase plasma calcium concentration.
Calcitriol
PTH
What are the 2 direct effects of PTH?
Increased mobilisation of Ca2+ in bone
Increased Ca2+ reabsorption in the kidneys + stimulation of 1-alpha-hydroxylase
What are the 2 direct effects of calcitriol?
Increased calcium absorption from the small intestine
Increased mobilisation of calcium in bone
What can stimulate PTH release?
Hypocalcaemia
State 4 signs of hypocalcaemia.
Parasthesia Convulsions Arrhythmias Tetany (CATs go numb!)
State 2 clinical signs of neuromuscular irritability due to hypocalcaemia.
Chvostek’s Sign Tap the facial nerve just below the zygomatic arch Positive = twitching of facial muscles Trousseau’s Sign Inflate BP cuff for several minutes Induces carpopedal spasm
State 4 causes of hypocalcaemia.
Hypoparathyroidism (e.g. due to surgery, AI or magnesium deficiency) Vitamin D deficiency Pseudohypoparathyroidism Renal failure (impaired 1-alpha-hydroxylase)
What are the 3 main signs and symptoms of hypercalcaemia?
Stones, abdominal moans + psychic groans
Stones (renal effects)
Polyuria + polydipsia
Nephrocalcinosis = deposition of calcium in the kidneys, renal colic, chronic renal failure
Abdominal moans (GI effects)
Anorexia, nausea, constipation, pancreatitis, dyspepsia
Psychic groans (CNS effects)
Fatigue, depression, impaired concentration, altered mentation, coma
What are the 2 main causes of hypercalcaemia?
Primary Hyperparathyroidism (e.g. parathyroid adenoma) Malignancy (e.g. bone tumours/metastases –> increased bone turnover –> increased plasma Ca2+; tumours can also produce PTH-like peptide)
State 2 other causes of hypercalcaemia.
Conditions of increased bone turnover (e.g. hyperthyroidism, Paget’s)
Vitamin D excess (rare)
Describe how you would differentiate between primary hyperparathyroidism and malignancy causing hypercalcaemia.
Primary hyperparathyroidism: no negative feedback because the parathyroid adenoma will be producing PTH autonomously
Plasma Calcium = HIGH
PTH = HIGH
In malignancy, negative feedback will be intact as it is due to increased bone turnover due to bony metastases
Plasma Calcium = HIGH
PTH = LOW
Describe the treatment of vitamin D deficiency in the case of normal renal function.
Give 25-hydroxy vitamin D
In inactive form of:
Ergocalciferol = 25-hydroxy vitamin D2
Cholecalciferol = 25-hydroxy vitamin D3
Describe the treatment of vitamin D deficiency in the case of renal failure.
Alfacalcidol = 1-hydroxycholecalciferol
as inadequate 1-alpha-hydroxylation
Where is phosphate reabsorbed? Via what?
Gut
Kidneys
Via Sodium-Phosphate transporter cells
How does PTH effect phosphate reabsorption?
Inhibits sodium phosphate transporter in proximal convoluted tubule cells
Phosphate is lost in urine
How does FGF 23 effect phosphate reabsorption?
Inhibits sodium phosphate transporter in proximal convoluted tubule cells
Inhibits synthesis of calcitriol, causing less phosphate absorption from gut
Describe regulation of high serum calcium
Ca2+ binds to calcium sensing receptor on PTH cell
Inhibits stimulation + release of PTH secretion
Describe regulation of low serum calcium
No binding to calcium sensing receptor on PTH cell
No inhibition
PTH is secreted
PTH action in body leads to increased Ca2+
In which 2 ways may vitamin D be obtained?
Through diet (Ergocalciferol- inactive) Exposure to sunlight (UVB): stimulates synthesis of 25 OH-Vit D3
How do changes in EC Ca2+ affect nerve + skeletal muscle excitability?
High: Ca2+ blocks Na+ influx, so less membrane excitability
Low: enables greater Na+ influx, so more membrane excitability
Describe calcium, phosphate and PTH levels in primary hyperparathyroidism
Calcium: High
Phosphate: Low
PTH: High (unsuppressed)
