Clinical Aspects of Calcium Homeostasis Flashcards
Sources of calcium
Dairy foods Green leafy vegetables Soya beans Tofu Nuts Bread Fish where you eat the bones
Functions of calcium
Bone formation
Cell division and growth
Muscle contraction
Neurotransmitter disease
What proportion of calcium is bound in plasma?
45% bound (mainly to albumin)
10% non ionised or complexed to citrate etc
45% ionised (BIOLOGICALLY IMPORTANT)
Normal range of plasma calcium
2.20 - 2.60 mmol/l
Acidosis and calcium
Acidosis increases ionised calcium thus predisposing to hypercalcaemia
Sources of vitamin D
oily fish; salmon, sardines, marcel Eggs Fortified fat spreads Fortified breakfast serials Some powdered milks
How are alterations in ECF Ca2+ levels transmitted to the parathyroid cells?
Via calcium sensing receptor (CSR)
An increase in Ca2+ does what to PTH levels?
Decreases
A decrease in Ca2+ leads to what in PTH levels?
An increase
What does PTH do?
Promotes reabsorption of calcium from renal tubules and bone
Mediates renal conversion of Vit D from its inactive to its active form
What serum calcium is classed as hypocalcaemia?
< 2.20
Presentation of hypocalcaemia
Neuromuscular irritability (tetany) Paraesthesia Carpopedal spasm Muscle twitching Trousseau's sign / Chovsteks sign (twitching of facial muscles after tapping on facial nerve) Seizures Layngo/bronchospasm Prolonged QT interval Hypotension Hear failure Arrythmia Papilloedema if chronic - Ectopic calcification (basal ganglion) - extrapyramidal signs - Parkinsonism - Dementia - Subcapsular cataracts - Abnormal dentition - Dry skin
Causes of hypocalcaemia
Total thyroidectomy Selective parathyroidectomy (transient and mild) Severe Vit D deficiency Mg2+ deficiency Cytotoxic drug induced hypocalcaemia Pancreatitis Large volume blood transfusions Rhabdomyolysis
Causes of hypoparathyroidism
Genetic disorders
Post surgical (thyroidectomy, parathyroidectomy, radial neck dissection)
Autoimmune
Infiltration of gland (iron overload, metastases, granulomatous)
Radiation induced destruction of gland
Hungry bone syndrome post parathyroidectomy
HIV
Agenesis (e.g. DiGeorge syndrome)
Resistance to PTH
Reduced secretion of PTH (neonatal hypocalcaemia, hypomagnesemia)
Causes of secondary hyperparathyroidism in response to hypocalcaemia
vit D deficiency or resistance Pseudohypoparathyroidism Hypomagnesemia Renal disease Tumour lysis Acute pancreatitis Acute respiratory alkalosis
Drugs causing hypocalcaemia
Inhibitors of bone resorption (bisphosphonates, calcitonin, denosumab)
Cincalcet
Calcium chelators (EDTA, citrate)
Foscarnet (complexes with calcium)
Phenytoin (converts vit D to inactive metabolites)
Fluoride poisoning
Investigations for hypocalcaemia
ECG serum calcium albumin phosphate PTH U and Es Vit D Mg
When does pseudohypoparathyroidism present?
Childhood
Definition of pseudohypoparathyroidism
A group of heterogeneous disorders defined by target organ (kidney and bone) unresponsiveness to PTH
Blood levels of pseudohypoparathyroidism
Hypocalcaemia
Hyperphosphatemia
Elevated PTH concentrations
What condition can occur in patients with pseudohypoparathyroidism?
Albright’s Hereditary Osteodystrophy (AHO)
Presentation of Albright’s Hereditary Osteodystrophy (AHO)
Obesity
Short stature
Shortening of metacarpal bones
What is pseudo-pseudoparahypothyroidism
AHO alone without abnormalities of calcium or parathyroid hormone
Treatment of “mild” hypocalcaemia
Oral calcium tablets
If vit D deficient start vit D
If low Mg2+, stop any precipitating drug and replace Mg2+
What is classed as “mild” hypocalcaemia?
Asymptomatic
> 1.9 mmol/L
What is classed as “severe” hypocalcaemia?
Symptomatic
< 1.9mmol/L
What can severe hypocalcaemia be classified as?
A medical emergency
Treatment of severe hypocalcaemia
IV calcium gluconate
Treat underlying cause
How much IV calcium gluconate is given in severe hypocalcaemia?
10-20ml 10% calcium gluconate in 50-100ml of 5% dextrose IV
What should also be prescribed in addition to vit D supplements if the patient has severe renal impairment?
Aldacalcidol or calcitriol
What hypercalcaemia level requires urgent correction due to risk of dysrhythmia and coma?
> 3.5mmol/L
What level of hypercalcaemia is usually asymptomatic?
<3.0mmol/L
Causes of acute hypercalcaemia
Primary hyperparathyroidism (sporadic) MEN syndromes Familial associated hyperparathyroidism Jaw tumour syndrome Familial hypocalciuric hypercalcaemia Tertiary hyperparathyroidism (renal failure) Hypercalcaemia of malignancy Vitamin D intoxication Chronic granulomatous disorders e.g. sarcoid, TB Medications Hyperthyroidism Acromegaly Phenochromocytoma Adrenal insufficiency Immobilisation Parenteral nutrition Milk alkali syndrome
Medications that cause acute hypercalcaemia
Thiazide diuretics
Lithium
Excessive vit A
Teriparatide
Phase to remember the presentation of hypercalcaemia
Bones, Stones, Groans and Psychic Moans
Presentation of hypercalcaemia
Polyuria Polydipsia Nephrolithiasis Nephrocalcinosis Distal renal tubular acidosis Nephrogenic diabetes insipidus Acute and chronic renal dysfunction Anorexia Nausea and vomiting Bowel hypomotility and constipation Pancreatitis Peptic Ulcer disease Muscle weakness Bone pain Osteopenia/osteoporosis Decreased concentration Confusion Fatigue Stupor, coma Shortening of QT interval Bradycardia Hypertension
Investigations of hypercalcaemia
U and Es Ca PO4 Alk phos Myeloma screen Serum ACE for sarcoidosis PTH
Who gets primary hyperparathyroidism?
F > M 3:1
50-60 years peak
Symptom of most patients at diagnosis of primary hyperparathyroidism
Asymptomatic
Types of tumours of parathyroid glands
85% parathyroid adenoma
15% four gland hyperplasia
<1% MEN type 1 or 2A
<1% parathyroid carcinoma
Presentation of hyperparathyroidism
Asymptomatic (most common)
Bone disease
Nephrolithiasis
What is nephrolithiasis?
Kidney stones
Investigations of hyperparathyroidism
Ca, PTH U and Es Abdominal imaging DEXA 24 urine collection for calcium excluding FHH Vitamin D Thyroid USS SESTAMBI
What is SESTAMBI?
Nuclear medicine scan
Treatment of hyperparathyroidism
Generous fluid intake
Cinacalcet
Surgery
Indications of parathyroid surgery
Serum calcium > 0.25 mmol/L above the upper limit of normal
Osteoporosis on DEXA
EGFR < 60 OR presence of kidney stones
Age < 50
What does cinacalcet do?
Acts as an calcimetic i.e. mimics the effect of calcium on the calcium sensing receptor on chief cells, this leads to a fall in PTH and subsequently calcium levels
What is familial hypocalciuric hypercalcaemia?
Autosomal dominant disorder of the calcium sensing receptor
Treatment of familial hypocalciuric hypercalcaemia
Benign so no therapy indicated
Typical tumours causing local osteolytic hypercalcaemia
breast cancer
multiple myeloma
lymphoma
Typical tumours causing humoral hypercalcaemia of malignancy
Squamous cell cancer (E.g. head and neck, oesophagus, cervix or lung) Renal Ovarian Endometrial Breast
The 3 Ps of MEN type 1
Primary hyperparathyroidism
Pancreatic
Pituitary
What % of MEN1 patients will have hyperparathyroidism?
> 95%
What mutation is MEN1?
MENIN mutation (chromosome 11)
When does MEN1 present?
2nd to 4th decade of life
What can MEN Type 2A cause?
Medullary thyroid cancer
Phaechromocytoma
Primary hyperparathyroidism
What mutation is in MEN Type 2A?
RET mutation
What % of Men Type 2A patients have hyperparathyroidism?
20-30%`
Which of MEN types is usually milder?
MEN 2A
Treatment of hypercalcaemia
Rehydration - 0.9% saline 4-6 litres over 24 hours IV bisphosphonates 2nd line - glucocorticoids - calcitonin - calcimimetics - parathyroidectomy
What systemic autoimmune disease causes hypercalcaemia?
Sarcoidosis
What is trosseaus sign?
Carpal spasm on inflation of BP cuff to pressure above systolic
What may the PTH level in primary hyperparathyroidism be?
Normal
