Calcium Flashcards
- Why is the calcium level in the blood so tightly controlled?
Nerves and muscles rely on calcium to cause depolarisation
- What are the consequences of high and low plasma calcium for nerve conduction?
High calcium – failure of depolarisation
Low calcium – trigger happy neurological system leading to epilepsy
- What is the normal range for plasma calcium concentration?
2.2-2.6 mmol/L
- What are the three forms in which calcium is present in the plasma?
Free (ionised) – 50% - biologically active
Protein-bound – 40% - bound to albumin
Complexed – 10% - citrate/phosphate
- State the equation for corrected calcium.
Corrected calcium = serum calcium + (0.02 x (40 – serum albumin in g/L))
NOTE: if your albumin level is constant, the total serum calcium will be roughly double the concentration of free calcium
- What are the main effects of PTH?
Liberation of calcium from the bone (increased bone breakdown) and kidneys (increased calcium resorption)
Stimulates 1-hydroxylase activity resulting in increased activated vitamin D
Stimulates renal phosphate excretion
- What is the rate-limiting step in vitamin D activation?
1alpha-hydroxylase
- What are the two forms of vitamin D?
Vitamin D2 (ergocalciferol) – from plants Vitamin D3 (cholecalciferol) – produced when UV hits the skin and converts 7-dehydrocholesterol to cholecalciferol NOTE: both are active
- Outline how 7-dehydrocholesterol is converted to activated vitamin D.
UV converts 7-dehydrocholesterol to cholecalciferol
This is then converted by 25-hydroxylase in the liver to 25-hydroxycholecalciferol
This then gets converted by 1-hydroxylase in the kidneys to 1,25-dihydroxycholecalciferol
NOTE: when you measure vitamin D levels, you’re actually measuring 25-hydroxy vitamin D levels. 25-hydroxy vitamin D is stored and converted to the active form when needed under the influence of PTH
- How can sarcoidosis lead to hypercalcaemia?
Lung cells of sarcoid tissue express 1-hydroxylase
NOTE: hypercalcaemia tends to be seasonal (i.e. during the summer months when more sunlight means more vitamin D which can be activated
- What are the main roles of vitamin D?
Increased intestinal calcium absorption
Increased intestinal phosphate absorption
Critical for bone formation
- What is ALP?
By-product of osteoblast activity
- What is bone a reservoir of?
Calcium
Phosphate
Magnesium
- What disease states does vitamin D deficiency cause?
Osteomalacia
Rickets
- List some risk factors for vitamin D deficiency.
Lack of sunlight
Dark skin
Dietary
Malabsorption
- Outline some clinical features of osteomalacia.
Bone and muscle pain
Increased fracture risk
Looser’s zones
- Outline the biochemical changes in osteomalacia.
Low calcium
Low phosphate
High ALP
- List some clinical features of rickets.
Bowed legs
Costochondral swelling
Widened epiphyses of the wrists
Myopathy
- Outline the pathophysiology of osteomalacia.
Vitamin D deficiency leads to secondary hyperparathyroidism which stimulates the liberation of calcium from the bone (leading to demineralisation of the bone)
- How can renal failure cause vitamin D deficiency?
A lack of 1alpha-hydroxylase means that you are unable to activate vitamin D
- Which group of drugs is associated with vitamin D deficiency?
Anticonvulsants – promote the breakdown of vitamin D
- Which component of common foods chelates vitamin D in the gut?
Phytic acid – food like chapatis have a high level of phytic acid which chelates vitamin D in the gut and reduces absorption
- How does acromegaly lead to osteoporosis?
Causes testosterone deficiency
- Describe the changes in serum biochemistry in osteoporosis.
Normal
- What is the main investigation used for osteoporosis?
DEXA scan
- Define:
a. T-score
b. Z score
a. T-score
Number of standard deviations from the mean of a young healthy population
b. Z-score
Number of standard deviations from the age-matched control
- List some causes of osteoporosis.
Age-related decline in bone mass Early menopause Sedentary lifestyle Alcohol Low BMI Thyrotoxicosis Hyperprolactinaemia Cushing’s syndrome Prolonged recurrent illness
- List some lifestyle changes that are recommended in the treatment of osteoporosis.
Weight-bearing exercise
Stop smoking
Reduce alcohol consumption
- List some drugs that may be used in the treatment of osteoporosis.
Vitamin D Bisphosphonates Teriparatide (PTH derivative) Strontium (anabolic and anti-resorptive) HRT SERMs (e.g. raloxifene)
- List some symptoms of hypercalcaemia.
Polyuria/polydipsia
Constipation
Confusion, seizures, coma
NOTE: these tend to occur when calcium level > 3 mmol/L
- What are the main causes of primary hyperparathyroidism?
Parathyroid adenoma
Parathyroid hyperplasia (associated with MEN1)
Parathyroid carcinoma
- Outline the serum biochemistry features of primary hyperparathyroidism.
High calcium Inappropriately raised PTH Low phosphate (‘phosphate trashing hormone’)
- Outline the pathophysiology of familial benign hypercalcaemia.
A mutation in the calcium-sensing receptor (CaSR) leads to an increase in the set-point for PTH release (leads to mild hypercalcaemia)
- Why don’t patients with familial benign hypercalcaemia get kidney stones?
PTH causes increased renal calcium absorption, thereby reducing urine calcium
- What are the three types of hypercalcaemia of malignancy?
Humoral hypercalcaemia of malignancy (e.g. small cell lung cancer) caused by PTHrP release Bone metastases (e.g. breast cancer) caused by local bone osteolysis Haematological malignancy (e.g. myeloma) caused by cytokines
- List some other non-PTH driven causes of hypercalcaemia.
Sarcoidosis
Thyrotoxicosis (increases bone resorption)
Hypoadrenalism (renal Ca2+ transport)
Thiazide diuretics (renal Ca2+ transport)
Excess vitamin D (e.g. sun beds)
- Outline the management of hypercalcaemia.
Fluids, fluids and more fluids
Bisphosphonates (stops cancer from eating bone)
Treat the underlying cause
