Calcium Disorders Flashcards
Calcium function
Bone mineralization
Blood clotting
Muscle contraction
Nerve function + neurotransmission
Serum calcium levels
2.2-2.6 mmol/L
Calcium state
Most serum calcium bound to plasma proteins (mainly albumin)
Only unbound calcium is biologically active
Serum calcium always needs to be corrected for albumin concentration
Serum calcium + albumin conc
+/- 0.02 mmol/L for every gram that albumin is below/above 40g/dL
Calcium hormonal regulation
Vitamin D
Parathyroid hormone
(calcitonin)
Vitamin D conversion
Vitamin D3 (cholecalciferol) - synthesizes in sun-exposed epidermis
Requires 2 activation (hydroxylation) steps
Liver- 25 hydroxycholecalciferol (majority Vit D in this form)
Kidney- 1,25-dihydroxycholecalciferol (calcitriol)
Majority of Vit D is in this form
25-hydroxycholecalciferol
Vit D bound
25-dihydroxycholecalciferol mostly bound to plasma proteins
1,25-dihydroxycholecalciferol largely unbound
1,25-dihydroxycholecalciferol half life
Short
15 hours
Calcitriol binds to
Nuclear vitamin D receptors
Vit D in Gut
Vit D increases the absorption of dietary calcium and phosphate
Vit D in kidney
Increases calcium and phosphate reabsorption
Vit D in bone
Stimulates osteoclasts to release calcium and phosphate
Parathyroid gland
4 parathyroid glands
PTH
Secreted by chief cells within parathyroid gland
Released in response to low calcium levels
Can also be stimulated by changes in phosphate concentration
Acts to increase serum Ca
PTH on Kidney
Increases Vit D
Increases Ca and Hydrogen reabsorption
Decreases phosphate and bicarbonate reabsorption
PTH on bone
Inhibits osteoblasts
Stimulates osteoclasts
Parathyroid-related peptide (PTHrP)
Acts via same cell surface receptor as PTH
Synthesised by placenta + breast, where it contributes to 1 alpha hydroxylation
Calcitonin
Secreted by parafollicular C cells of thyroid
In response to raised serum calcium
Acts on renal tubules to reduce calcium and phosphate reabsorption
Inhibits osteoclasts
Hypocalcaemia signs and symptoms
Muscle cramps
Trousseau’s sign- carpopedal spasm when applying BP cuff
Tetany and neuromuscular excitability
Chvostek’s sign- tapping over the facial nerve causes facial muscles to twitch
Mood swings
Convulsions
Cardiac arrhythmias
Hypocalcaemia causes- hypoparathyroidism
Surgical removal (thyroidectomy)
Autoimmune damage
Congenital (De George Syndrome agenesis of the parathyroid)
Hypocalcaemia causes- not hypoparathyroidism
Hypomagnesaemia Renal failure (PTH can no longer increase Vit D hydroxylation, and hypocalcaemia can develop) PTH resistance (aka pseudohypoparathyroidism)
Hypocalcaemia treatment
Oral calcium
Calcitriol
Hypercalcaemia signs and symptoms
Tiredness + fatigue Anorexia + nausea Thirst + polyuria Muscle weakness Headache Body pain Renal stones Abdo pain (constipation, pancreatitis) Mood disturbance Cardiac arrhythmias
Hypercalcaemia causes
Primary hyperparathyroidism Malignancy Drugs and diet Familial benign hypercalcaemia Granulomatous disease- Sarcoidosis Tertiary hyperparathyroidism
Primary hyperparathyroidism
Relatively common
80% single parathyroid adenoma (remainder hypertrophy of more than one gland)
Parathyroid malignancy rare
If parathyroid malignancy found in patients <45, consider..
MEN syndrome
Hypercalcaemia- malignancy that secretes PTHrP
Classically squamous lung cell cancer
Hypercalcaemia- malignancy
Malignancy that secretes PTHrP
Bone metastases
Multiple myeloma- sclerotic bone lesions
Hypercalcaemia- secondary hyperparathyroidism
Usually in renal failure context
Lack activation of Vit D, with hypocalcaemia, as well as increased phosphate levels stimulate the parathyroid gland to increase production to compensate
Hypercalcaemia- tertiary hyperparathyroidism
With prolonged secretion of parathyroid hormone, the glands may become autonomous
Over secrete PTH even when calcium levels have normalised
Hypercalcaemia causes- drugs and diets
Thiazide diuretics - increased calcium reabsorption from distal tubule
Vit D overdose
Hypercalcamia Causes- familial benign hypercalcaemia
AKA familial hypocalciuric hypercalcaemia (FHH) Autosomal dominant Defective calcium receptor on PT gland Leads to reduce negative feedback --> elevated PTH and calcium Elevated PTH causes hypocalciuria FHH doesn't need treatment
Hypercalcamia causes- sarcoid and GH
Non-caseating granulomas can have 1 alpha hydroxylase activity
GH can also stimulate renal alpha 1 hydroxylase activity
Hypercalcaemia investigations
Serum Ca and phosphate
PTH- primary, tertiary or FHH: high or inappropriately “normal” in context of elevated calcium
Vit D (PTH raised in Vit D deficiency)
24 hr urinary Ca collection
Hypercalcaemia investigations- primary hyperparathyroidism
Imaging of parathyroid- CT or MRI, isotope uptake scan
Venous sampling
Hypercalcaemia investigations- other
Look for malignancy- XR chest, CT
Urinary Bence Jones proteins
Serum ACE
Hypercalcaemia treatment- Severe
EMERGENCY
IV rehydration
IV biphosphonates (e.g. pamidronate)
Steroids in haematological malignancy or sarcoidosis
Hypercalcaemia treatment- mild
Can monitor as rarely worsens
Hypercalcaemia- surgery
Considered when complications:
Renal impairment
Stones
Bone demineralisation
