Clinical Aspects of Calcium Homeostasis Flashcards

1
Q

Sources of calcium

A
Dairy foods
Green leafy vegetables
Soya beans
Tofu 
Nuts
Bread 
Fish where you eat the bones
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2
Q

Functions of calcium

A

Bone formation
Cell division and growth
Muscle contraction
Neurotransmitter disease

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3
Q

What proportion of calcium is bound in plasma?

A

45% bound (mainly to albumin)
10% non ionised or complexed to citrate etc
45% ionised (BIOLOGICALLY IMPORTANT)

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4
Q

Normal range of plasma calcium

A

2.20 - 2.60 mmol/l

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5
Q

Acidosis and calcium

A

Acidosis increases ionised calcium thus predisposing to hypercalcaemia

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6
Q

Sources of vitamin D

A
oily fish; salmon, sardines, marcel 
Eggs
Fortified fat spreads
Fortified breakfast serials
Some powdered milks
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7
Q

How are alterations in ECF Ca2+ levels transmitted to the parathyroid cells?

A

Via calcium sensing receptor (CSR)

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8
Q

An increase in Ca2+ does what to PTH levels?

A

Decreases

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9
Q

A decrease in Ca2+ leads to what in PTH levels?

A

An increase

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10
Q

What does PTH do?

A

Promotes reabsorption of calcium from renal tubules and bone

Mediates renal conversion of Vit D from its inactive to its active form

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11
Q

What serum calcium is classed as hypocalcaemia?

A

< 2.20

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12
Q

Presentation of hypocalcaemia

A
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
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13
Q

Causes of hypocalcaemia

A
Total thyroidectomy
Selective parathyroidectomy (transient and mild)
Severe Vit D deficiency
Mg2+ deficiency 
Cytotoxic drug induced hypocalcaemia
Pancreatitis
Large volume blood transfusions
Rhabdomyolysis
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14
Q

Causes of hypoparathyroidism

A

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)

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15
Q

Causes of secondary hyperparathyroidism in response to hypocalcaemia

A
vit D deficiency or resistance
Pseudohypoparathyroidism 
Hypomagnesemia
Renal disease
Tumour lysis
Acute pancreatitis
Acute respiratory alkalosis
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16
Q

Drugs causing hypocalcaemia

A

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

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17
Q

Investigations for hypocalcaemia

A
ECG
serum calcium 
albumin 
phosphate 
PTH
U and Es
Vit D
Mg
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18
Q

When does pseudohypoparathyroidism present?

A

Childhood

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19
Q

Definition of pseudohypoparathyroidism

A

A group of heterogeneous disorders defined by target organ (kidney and bone) unresponsiveness to PTH

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20
Q

Blood levels of pseudohypoparathyroidism

A

Hypocalcaemia
Hyperphosphatemia
Elevated PTH concentrations

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21
Q

What condition can occur in patients with pseudohypoparathyroidism?

A

Albright’s Hereditary Osteodystrophy (AHO)

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22
Q

Presentation of Albright’s Hereditary Osteodystrophy (AHO)

A

Obesity
Short stature
Shortening of metacarpal bones

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23
Q

What is pseudo-pseudoparahypothyroidism

A

AHO alone without abnormalities of calcium or parathyroid hormone

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24
Q

Treatment of “mild” hypocalcaemia

A

Oral calcium tablets
If vit D deficient start vit D
If low Mg2+, stop any precipitating drug and replace Mg2+

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25
Q

What is classed as “mild” hypocalcaemia?

A

Asymptomatic

> 1.9 mmol/L

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26
Q

What is classed as “severe” hypocalcaemia?

A

Symptomatic

< 1.9mmol/L

27
Q

What can severe hypocalcaemia be classified as?

A

A medical emergency

28
Q

Treatment of severe hypocalcaemia

A

IV calcium gluconate

Treat underlying cause

29
Q

How much IV calcium gluconate is given in severe hypocalcaemia?

A

10-20ml 10% calcium gluconate in 50-100ml of 5% dextrose IV

30
Q

What should also be prescribed in addition to vit D supplements if the patient has severe renal impairment?

A

Aldacalcidol or calcitriol

31
Q

What hypercalcaemia level requires urgent correction due to risk of dysrhythmia and coma?

A

> 3.5mmol/L

32
Q

What level of hypercalcaemia is usually asymptomatic?

A

<3.0mmol/L

33
Q

Causes of acute hypercalcaemia

A
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
34
Q

Medications that cause acute hypercalcaemia

A

Thiazide diuretics
Lithium
Excessive vit A
Teriparatide

35
Q

Phase to remember the presentation of hypercalcaemia

A

Bones, Stones, Groans and Psychic Moans

36
Q

Presentation of hypercalcaemia

A
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
37
Q

Investigations of hypercalcaemia

A
U and Es
Ca
PO4
Alk phos
Myeloma screen
Serum ACE for sarcoidosis
PTH
38
Q

Who gets primary hyperparathyroidism?

A

F > M 3:1

50-60 years peak

39
Q

Symptom of most patients at diagnosis of primary hyperparathyroidism

A

Asymptomatic

40
Q

Types of tumours of parathyroid glands

A

85% parathyroid adenoma
15% four gland hyperplasia
<1% MEN type 1 or 2A
<1% parathyroid carcinoma

41
Q

Presentation of hyperparathyroidism

A

Asymptomatic (most common)
Bone disease
Nephrolithiasis

42
Q

What is nephrolithiasis?

A

Kidney stones

43
Q

Investigations of hyperparathyroidism

A
Ca, PTH
U and Es
Abdominal imaging
DEXA
24 urine collection for calcium excluding FHH
Vitamin D
Thyroid USS
SESTAMBI
44
Q

What is SESTAMBI?

A

Nuclear medicine scan

45
Q

Treatment of hyperparathyroidism

A

Generous fluid intake
Cinacalcet
Surgery

46
Q

Indications of parathyroid surgery

A

Serum calcium > 0.25 mmol/L above the upper limit of normal
Osteoporosis on DEXA
EGFR < 60 OR presence of kidney stones
Age < 50

47
Q

What does cinacalcet do?

A

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

48
Q

What is familial hypocalciuric hypercalcaemia?

A

Autosomal dominant disorder of the calcium sensing receptor

49
Q

Treatment of familial hypocalciuric hypercalcaemia

A

Benign so no therapy indicated

50
Q

Typical tumours causing local osteolytic hypercalcaemia

A

breast cancer
multiple myeloma
lymphoma

51
Q

Typical tumours causing humoral hypercalcaemia of malignancy

A
Squamous cell cancer (E.g. head and neck, oesophagus, cervix or lung) 
Renal 
Ovarian 
Endometrial 
Breast
52
Q

The 3 Ps of MEN type 1

A

Primary hyperparathyroidism
Pancreatic
Pituitary

53
Q

What % of MEN1 patients will have hyperparathyroidism?

A

> 95%

54
Q

What mutation is MEN1?

A

MENIN mutation (chromosome 11)

55
Q

When does MEN1 present?

A

2nd to 4th decade of life

56
Q

What can MEN Type 2A cause?

A

Medullary thyroid cancer
Phaechromocytoma
Primary hyperparathyroidism

57
Q

What mutation is in MEN Type 2A?

A

RET mutation

58
Q

What % of Men Type 2A patients have hyperparathyroidism?

A

20-30%`

59
Q

Which of MEN types is usually milder?

A

MEN 2A

60
Q

Treatment of hypercalcaemia

A
Rehydration - 0.9% saline 4-6 litres over 24 hours 
IV bisphosphonates 
2nd line
- glucocorticoids 
- calcitonin 
- calcimimetics
- parathyroidectomy
61
Q

What systemic autoimmune disease causes hypercalcaemia?

A

Sarcoidosis

62
Q

What is trosseaus sign?

A

Carpal spasm on inflation of BP cuff to pressure above systolic

63
Q

What may the PTH level in primary hyperparathyroidism be?

A

Normal