1b Calcium Dysregulation Flashcards
What are the two hormones which increase serum calcium?
Vitamind D and Parathyroid hormone
What are the three places in which the regulators of serum calcium act?
Kidney, bone and the gut
What hormone acts to decrease serum calcium?
Calcitonin
Where is calcitonin secreted from?
The thyroid parafollicular cells
What effect does calcitonin have on serum calcium?
Reduces calcium acutely - however no negative effect if the parafollicular cells are removed eg thyroidectomy
What is tested for when a patients vitamin D levels are measured?
Serum 25-OH Vitamin D
How does calcitriol regulate its own synthesis?
it decreases transcription of 1-alpha hydroxylase
Describe how calcitriol is produced?
UVB from sun
7 dehydrocholesterol
Pre-vitamin D3 to Vitamin D3
D3 converted to 25 (OH) Cholecalciferol using 25-hydroxylase
Then to 1,25 (OH)2 cholecalciferol using 1 alpha-hydroxylase
Where is 25 hydroxylase found?
Liver
Where is 1-alpha hydroxylase found?
In the kidney
Which form of vitamin D is found in the diet?
D2
What are the effects of calcitriol on the kidneys?
Increased calcium and Phosphate reabsorption
What are the effects of calcitriol on the gut?
Increased phosphate and calcium absorption
What are the effects of calcitriol on the bone?
Increased osteoblast activity - bone building
What are the effects of PTH on the kidney?
Increased Calcium reabsorption and phosphate excretion and 1-alpha hydroxylase activity
What impact does PTH have on the gut?
The increased 1-alpha hydroxylase activity leads to more vitamin D, therefore more calcium and phosphate absorption
What is the effect of PTH on the bone?
Increased Calcium resorption from the bone
Why is the net effect on phosphate 0?
PTH = Excretion
Vitamin D = Reabsorption therefore overall effect is zero
What is the effect of FGF23?
Increases phosphate excretion
How does FGF23 work?
It inhibits the Na+/PO4 3- co transporter in the apical membrane of the proximal tubule, therefore more phosphate in the filtrate being excreted
What is the effect on FGF23 on calcitriol?
It inhibits the effects of calcitriol, leading to less phosphate reabsorption from the gut
What is chvosteks sign?
Facial paraesthesia - when tapping the zygomatic arch
What is trousseau’s sign?
When inflating a blood pressure cuff, the wrist = tetany = unable to relax a contracted wrist
What are the signs and symptoms of hypocalcaemia?
Convulsions
Arrhythmias
Tetany - involuntary contractions
Paraethesia - tingling and numbness
What are the causes of hypocalcaemia?
Low PTH
- neck surgery
- autoimmune
- magnesium deficiency
- congenital
Low Vitamin D
- deficiency
- poor metabolism
- lack of sunshine
- renal failure
What are the signs and symptoms of hypercalcaemia?
Stones, abdominal moans and psychic groans and reduced neuronal excitability
- kidney stones
- constipation, pancreatitis, nausea
- Fatigue, depression, impaired concentration, low mood
What are the causes of hypercalcaemia?
Primary Hyperparathyroidism
Malignancy
Vitamin D excess
What is primary hyperparathyroidism?
When the patient has too much PTH, usually due to a Malignancy (parathyroid gland adenoma)
What happens to levels of PTH and Ca2+ in primary hyperparathyroidism?
they both increase
How do malignancies cause hyperparathyroidism?
Bony metastases produce local factors to activate osteoclasts = more bone breaking
Some cancers also secrete PTH related peptide which acts as PTH therefore higher Ca2+
What is the normal relationship between PTH and Calcium?
High PTH = Lower Ca2+
High PTH, and high Ca2+, what has happened?
Primary hyperparathyroidism
- Parathyroid adenoma which produced too much PTH
- Ca2+ also increases, but no negative feedback to reduce the Ca2+ therefore both are high
What happens to phosphate in primary hyperparathyroidism?
Low phosphate - increased renal phosphate excretion
What is the treatment of choice of primary hyperparathyroidism?
Parathyroidectomy - cut out the gland
What are the risks of untreated primary hyperparathyroidism?
osteoporosis
Renal calculi
Mental function reduced, mood
What is secondary hyperparathyroidism?
The normal physiological response to hypocalcaemia
What is the most common cause of secondary hyperparathyroidism?
Vitamin D deficiency, as lack of vitamin D = lower Ca2+, therefore PTH will rise to try increase Ca2+
Why can calcitriol not be made in renal failure?
renal 1-alpha-hydroxylase is not made, therefore no vitamin D
What is the treatment of choice in secondary hyperparathyroidism with patients with normal renal function?
Vitamin D replacement - give 25 hydroxy Vitamin D (inactive forms as the body can convert them itself)
What are the two forms of vitamin D?
Ergocalciferol - D2
Cholecalciferol - D3
What is the treatment of choice for primary hyperparathyroidism?
Parathyroidectomy is the treatment of choice
What is the treatment of choice in secondary hyperparathyroidism with patients with impaired renal function?
Alfacalcidol - already hydroxylaed vitamin D
What is tertiary hyperparathyroidism?
a complication of chronic renal failure, leading to chronic vit d deficiency - this leads to the parathyroid gland working extra hard to produce PTH that eventually hypertrophy of the gland occurs, which can lead to autonomous secretions of PTH
What is seen in tertiary hyperparathyroidism?
Initially, High PTH and low Ca2+, but overtime = Ca2+ rises
What is the treatment for tertiary hyperparathyroidism?
Parathyroidectomy
What is the normal PTH response to hypercalcaemia?
PTH to fall
What happens to PTH and calcium when you have hypercalcaemia due to malignancy?
High Calcium
Low / suppressed PTH
what are the differentials for hypercalcaemia with raised PTH?
If normal renal function - primary hyperparathyroidism
If chronic renal failure - tertiary hyperparathyroidism
What condition does a patient have if they have low Ca2+ and high PTH?
Secondary hyperparathyroidism = due to vitamin d deficiency
What is first line treatment for hypercalcaemia of malignancy?
- IV FLUIDS
- BISPHOSPHONATES
- SURGERY/CHEMO/RADIOTHERAPY
