Calcium Metabolism and Metabolic Bone Disease Flashcards by Francesca Siracusa

What are the main roles of calcium?

Skeleton - structure

Metabolism - action potentials and intracellular signalling

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What is the normal range of calcium?

2.2-2.6 mmol/L

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Where is most of calcium stored in the body?

Skeleton

99%

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In which 3 forms is serum calcium found?

Free = 50%, biologically active
Protein-bound = 40%, bound to albumin
Complexed = 10%, citrate or phophate

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How does albumin affect calcium?

If a person has low albumin, bound calcium will be low and free calcium will be normal. This means their uncorrected calcium will appear to be lower than normal. Check the corrected calcium.

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Which are the two main hormones involved in calcium homeostasis?

Parathyroid hormone and 1,25(OH)2 vitamin D

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What are the 3 sources from which PTH will obtain calcium?

Bone
Gut (absorption)
Kidneys (resorption and renal 1-alpha-hydroxylase activation)

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Which is the rate limiting step in vitamin D activation?

1-alpha-hydroxylase

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What are the 3 main roles of PTH?

Liberation of calcium from bone and kidneys
Stimulation of 1-alpha-hydroxylase activity which results in the production of calcitriol
Stimulates renal phosphate excretion

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What is needed for the initial step in vitamin D synthesis?

UV light from sun

Converts 7-dehydrocholesterol to cholecalciferol

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In which organ is 25-hydroxylase converted to 25-hydroxycholecalciferol?

Liver

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When vitamin D is measured in the blood, which form is being measured?

25-hydroxycholecalciferol

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In which organ is 25-hydroxycholecalciferol converted to 1,25(OH)2 vitamin D and which enzyme is involved?

Kidneys

1-alpha-hydroxylase

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What are the 3 main roles of activated vitamin D?

Increase intestinal calcium absorption
Increase intestinal phosphate absorption
Bone formation

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What are the two conditions caused by vitamin D deficiency?

Osteomalacia = adults
Rickets = children

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What main condition can cause osteomalacia?

Renal failure

Lack of 1-alpha-hydroxylase means vitamin D cannot be activated

Which endocrine abnormality will occur as a result of vitamin D deficiency?

Secondary hyperparathyroidism

Osteoporotic occurs as a result of ____.

Loss of bone mass

What will the biochemistry look like in osteoporosis?

Normal calcium and phosphate

Classification of osteoporosis using T and Z scores.

Osteoporosis = T-score < -2.5 
Osteopaenia = T-score between -1 and -2.5

Z score is useful to identify accelerated bone loss in younger patients, since they are compared to an age-matched control.

Causes of osteoporosis.

Age-related decline in bone mass
Failure to attain peak bone mass
More rapid bone loss during adulthood: 
- Early menopause
- Sedentary lifestyle
- Alcohol
- Low BMI
- Hyperprolactinaemia
- Thyrotoxicosis
- Cushing's syndrome
- Steroids
- Prolonged recurrent illness

How is osteoporosis treated?

Lifestyle:

exercise
stop smoking
reduce alcohol

Drugs:

vitamin D
bisphosphonates
strontium
HRT
SERMs (raloxifene)

What are the symptoms of primary hyperparathyroidism?

Bones = PTH bone disease
Stones = renal calculi
Moans = abdominal pain due to constipation, pancreatitis
Groans = psychiatric + neurological features = confusion, seizures, coma

What are the main causes of hypercalcaemia?

PTH suppressed:

Malignancy
Sarcoidosis
Vitamin D excess

PTH not supressed:
- Primary hyperparathyroidism

What are the causes of primary hyperparathyroidism?

Parathyroid adenoma Parathyroid hyperplasia Parathyroid carcinoma

What is the biochemistry in someone with primary hyperparathyroidism?

``` High calcium Inappropriately raised PTH Low phosphate (phosphate trashing hormone) ```

What is the main condition to differentiate in hypercalcaemia?

Familial benign hypercalcaemia | Benign mutation in the CaSR - calcium sensing receptor.

What are the 3 main types of hypercalcaemia in malignancy?

1. Humoral hypercalcaemia of malignancy (e.g. squamous cell lung cancer - PTHrP release) 2. Bone metastases (local bone osteolysis) 3. Haematological malignancy (e.g. myeloma)

List causes of non-PTH driven hypercalcaemia.

``` Sarcoidosis Thyrotoxicosis Hypoadrenalism Thiazide diuretics Excess vitamin D ```

Management of Hypercalcaemia

FLUIDS Bisphosphonates if cause is KNOWN TO BE cancer Treat underlying cause

Below what level is hypocalcaemia defined?

<2.2 mmol/L

What are the main clinical features of hypocalcaemia?

Neuromuscular excitability - Chvostek's sign (facial nerve) - Trousseau's sign (blood pressure cuff) - Hyperreflexia - Laryngeal spasm (stridor) - Convulsions

What are the causes of hypocalcaemia?

Normal or high PTH: - Vitamin D deficiency - Chronic kidney disease - PTH resistance (pseudohyperparathyroidism, will have high phosphate + low calcium) Low PTH: - Surgical (removal of parathyroid glands in thyroidectomy) - Autoimmune - Congenital (e.g. DiGeorge syndrome) - Magnesium deficiency

What is the biochemistry in osteomalacia?

Low calcium Low phosphate High ALP

What are the clinical features of children with Rickets?

Bowed legs Costochondral swelling Widened epiphyses (often at the wrists) Myopathy

What is Paget's disease of the bone?

One or more areas of aggressive osteoclast-mediated bone resorption followed by imperfect osteoblast-mediated bone repair

Which bones are frequently affected in Pagets disease of the bone?

Axial skeleton Femurs Tibias

What is the triad of renal osteodystrophy?

Secondary hyperparathyroidism Osteomalacia Vitamin D deficiency

What is parathyroid bone disease and what is the sequence of changes?

Primary hyperparathyroidism leading to loss of cortical bone. 1. Demineralisation 2. Osteitis fibrosa (bone resorption and peritrabecular fibrosis) 3. Osteitis fibrosa cystica (extensive bone resorption + marrow fibrosis, cysts within marrow spaces, brown tumours)