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endocrine system 1 > Clinical Calcium Homeostasis > Flashcards

Clinical Calcium Homeostasis Flashcards

1
Q

Give examples of dietary sources of calcium.

A
  • milk, cheese and other dairy foods
  • green leafy vegetables(broccoli, cabbage and okra)
  • soya beans
  • tofu
  • nuts
  • bread and anything made with fortified flour
  • fish (where you eat the boneseg such as sardines and pilchards)
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2
Q

What are the roles of calcium in the body

A
  • bone formation
  • cell division and growth
  • muscle contraction
  • neurotransmitter release
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3
Q

What happens to the calcium we intake?

A

Dietary intake 1000mg

  • 800mg faeces
  • 0.9% cells
  • 0.1% ECF
  • 200mg kidneys
  • 99% bone
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4
Q

What proportion of calcium is bound in plasma?

A
  • 45% bound (mainly to albumin)
  • 10% non-ionised or complexed to citrate, PO4 etc.
  • 45% ionised
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5
Q

What is the normal calcium range?

A

Normal range 2.20-2.60 mmol/l

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6
Q

How do we calculate free calcium?

A
  • Increased albumin decreases free calcium
  • Decreased albumin increases free calcium
  • Adjust Ca2+ by 0.1mmol/l for each 5g/l reduction in albumin from 40g/l
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7
Q

What conditions lead to hypercalcaemia?

A

Acidosis increases ionised calcium thus predisposing to hypercalcaemia

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8
Q

What are good food sources of vitamin D?

A
  • Oily fish– such as salmon, sardines and mackerel
  • Eggs
  • Fortified fat spreads
  • Fortified breakfast -Cereals
  • Some powdered milks
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9
Q

Where are the parathyroid glands located?

A

Posterior to the thyroid gland in the neck

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10
Q

How many parathyroid glands are there?

A

4

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11
Q

What kind of cells are in the parathyroid glands?

A

Chief cells

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12
Q

What do the parathyroid glands do?

A

Secrete PTH

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13
Q

What cells in the parathyroid gland respond directly to changes in calcium concentrations?

A

Chief cells

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14
Q

What happens to PTH when calcium rises?

A

Decreases

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15
Q

What happens to PTH when calcium falls?

A

Increases

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16
Q

When is PTH secreted?

A

PTH is secreted in response to a fall in calcium

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17
Q

How are alterations in ECF Ca levels transmitted into the parathyroid glands?

A

via calcium-sensing receptor (CaSR)

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18
Q

What are the direct effects of PTH?

A

promote reabsorption of calcium from renal tubules & bone

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19
Q

What does PTH mediate?

A

The renal conversion of vitamin D from its inactive to active form

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20
Q

What enzyme activates vitamin D?

A

25(OH) vitamin D 1α-hydroxylase

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21
Q

Why do some patients need activated vitamin D?

A

If they have renal failure they are unable to convert inactive vitamin D to active vitamin D

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22
Q

When do symptoms of hypocalcaemia typically develop?

A

when adjusted serum calcium levels fall below 1.9mmol/L

- this threshold does vary and is dependent on the rate of fall

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23
Q

What acute neuromuscular irritability (tetany) is associated with hypocalcaemia?

A
  • Paresthesia
  • Muscle twitching
  • Carpopedal spasm
  • Trosseau’s sign
  • Chovstek’s sign
  • Seizures
  • Laryngoscope
  • Bronchospasm
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24
Q

What acute cardiovascular symptoms are associated with hypocalcaemia?

A
  • Prolonged QT interval
  • Hypotension
  • Heart failure
  • Arrhythmia
  • Papilloedema
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25
Q

What chronic symptoms are associated with hypocalcaemia?

A
  • Ectopic calcification (basal ganglia)
  • Extrapyramidal signs
  • Parkinsonism
  • Dementia
  • Subcapsular cataracts
  • Abnormal dentition
  • Dry skin
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26
Q

-

A

-

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27
Q

What are the high PTH causes of hypocalcaemia?

A

secondary hyperparathyroidism in response to hypocalcemia

  • vitamin D deficiency or resistance
  • pseudohypoparathyroidism
  • hypomagnesemia
  • renal disease
  • tumour lysis
  • acute pancreatitis
  • acute respiratory alkalosis
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28
Q

What drugs can cause hypocalcaemia?

A
  • Inhibitors of bone resorption (bisphosphonates, calcitonin, denosumab)
  • Cinacalcet
  • Calcium chelators (EDTA, citrate, phosphate)
  • Foscarnet (due to intravascular complexing with calcium)
  • Phenytoin (due to conversion of vitamin D to inactive metabolites
  • Fluoride poisoning
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29
Q

What history is important in hypocalcaemia?

A
  • Symptoms
  • Ca and vitamin D intake
  • Neck surgery
  • Autoimmune disorders
  • Medications
  • Family history
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30
Q

What should be looked for on examination of hypocalcaemia?

A

Neck scars

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31
Q

What investigations should be carried out for hypocalcaemia?

A
  • ECG
  • Serum calcium
  • Albumin
  • Phosphate
  • PTH
  • U+Es
  • Vitamin D
  • Magnesium
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32
Q

How should hypocalcaemia be investigated if the PTH is low or normal?

A

Check magnesium

  • Low: magnesium deficiency
  • Normal: hypoparathyroidism or calcium sensing receptor defect (rare)
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33
Q

How should hypocalcaemia be investigated if the PTH is high?

A

Check urea and creatinine

  • Normal: check vit D (normal vit D suggest pseudohypoparathyroidism, or calcium deficiency) (low vit D suggests vit D deficiency)
  • High: renal failure
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34
Q

What are the levels of total calcium, ionised calcium, phosphate and PTH in: hypoalbuminaemia?

A
  • Total calcium: low
  • Ionised calcium: normal
  • Phosphate: normal
  • PTH: normal
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35
Q

What are the levels of total calcium, ionised calcium, phosphate and PTH in: alkalosis?

A
  • Total calcium: normal
  • Ionised calcium: low
  • Phosphate: normal
  • PTH: normal/high
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36
Q

What are the levels of total calcium, ionised calcium, phosphate and PTH in: chronic renal failure?

A
  • Total calcium: low
  • Ionised calcium: low
  • Phosphate: high
  • PTH: high
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37
Q

What are the levels of total calcium, ionised calcium, phosphate and PTH in: hypoparathyroidism?

A
  • Total calcium:low
  • Ionised calcium: low
  • Phosphate: high
  • PTH: low
38
Q

What are the levels of total calcium, ionised calcium, phosphate and PTH in: pseudohypoparathyroidism?

A
  • Total calcium: low
  • Ionised calcium: low
  • Phosphate: high
  • PTH: high
39
Q

What are the levels of total calcium, ionised calcium, phosphate and PTH in: acute pancreatitis?

A
  • Total calcium: low
  • Ionised calcium: low
  • Phosphate: low/normal
  • PTH: high
40
Q

What are the levels of total calcium, ionised calcium, phosphate and PTH in: hypomagnesium?

A
  • Total calcium: low
  • Ionised calcium: low
  • Phosphate: variable
  • PTH: low or normal
41
Q

What may hypoparathyroidism result from?

A
  • Agenesis (e.g. DiGeorge syndrome)
  • Destruction (neck surgery, autoimmune disease)
  • Infiltration (haemochromatosis, Wilson’s disease)
  • Reduced secretion of PTH (neonatal hypocalcaemia, hypomagnesaemia)
  • Resistance to PTH
42
Q

What is pseudohypoparathyroidism?

A

Pseudohypoparathyroidism, which presents in childhood, refers to a group of heterogenous disorders defined by target organ (kidney and bone) unresponsiveness to PTH.

43
Q

What is pseudohypoparathyroidism characterised by?

A

It is characterised by hypocalcaemia, hyperphosphatemia and in contrast to hypoparathyroidism, elevated rather than reduced PTH concentrations

44
Q

What can occur on some patients with pseudohypoparathyroidism?

A

Albright’s hereditary osteodystrophy (AHO)

45
Q

What are the features of Albright’s hereditary osteodystrophy (AHO)?

A
  • Obesity
  • Short stature,
  • Shortening of the metacarpal bones
46
Q

What is AHO alone without abnormalities of calcium or PTH called?

A

Pseudo-pseudohypoparathyroidism

47
Q

What is mild hypocalcaemia classed as?

A

Mild Hypocalcaemia (asymptomatic, >1.9mmo/L)

48
Q

What is the treatment for mild hypocalcaemia?

A
  • Commence oral calcium tablets
  • If post thyroidectomy repeat calcium 24 hours later
  • If vitamin D deficient, start vitamin D
  • If low Mg, stop any precipitating drug and replace Mg
49
Q

What is severe hypocalcaemia classed as?

A

Severe hypocalcaemia (symptomatic, <1.9mmol/L)

50
Q

What is the treatment for severe hypocalcaemia?

A
  • This is a medical emergency
  • Administer IV calcium gluconate
  • Initial bolus (10-20ml 10% calcium gluconate in 50-100ml of 5% dextrose IV over 10 minutes with ECH monitoring)
  • Calcium gluconate infusion
  • Treat the underlying cause
51
Q

Why should alfacalcidol or calcitriol be prescribed in patients with severe renal impairment?

A

Vitamin D requires hydroxylation by the kidney to its active form, therefore the hydroxylated derivatives alfacalcidol or calcitriol should be prescribed if patients with severe renal impairment require vitamin D therapy

52
Q

How should vitamin D replacement be administered?

A
  • Advice regarding dietary sources
  • Most tablets contain a combination of vitamin D and calcium
  • Maintenance dose ~400-1000 international units
  • Higher loading dose required (e.g. 3200 units daily for 12 weeks)
53
Q

What is classified as mild hypercalcaemia?

A

<3.0mmol/L

Often asymptomatic and does usually require urgent correction

54
Q

What is classified as moderate hypercalcaemia?

A

3.0-3.5mmol/L

May be well tolerated if it has risen slowly, but may be symptomatic and prompt treatment is usually indicated

55
Q

What is classified as severe hypercalcaemia?

A

> 3.5mmol/L

Requires urgent correction due to risk of dysrhythmia and coma

56
Q

Give examples of parathyroid mediated causes of hypercalcaemia.

A

-Primary hyperparathyroidism (sporadic)
-Inherited variants
Multiple endocrine neoplasia (MEN)
Familial isolated hyperparathyroidism
Hyperparathyroidism jaw tumour syndrome
-Familial hypocalciuric hypercalcaemia
-Tertiary hyperparathyroidism (renal

57
Q

Give examples of non-parathyroid mediated causes of hypercalcaemia.

A

-Hypercalcaemia of malignancy
-PTHrp
-Activation of extrarenal 1 alpha-hydroxylase (increased calcitriol)
-Osteolytic bone metastases and local cytokines
-Vitamin D intoxication
-Chronic granulomatous disorders
• Sarcoid
• TB
• Berylliosis
• Histoplasmosis
• Wegner’s

58
Q

Give examples of medications that can cause hypercalcaemia

A
  • Thiazide diuretics
  • Lithium
  • Teriparatide
  • Excessive vitamin A
  • Theophylline toxicity
59
Q

What miscellaneous causes of hypercalcaemia are there?

A
  • Hyperthyroidism
  • Acromegaly
  • Pheochromocytoma
  • Adrenal insufficiency
  • Immobilisation
  • Parenteral nutrition
  • Milk alkali syndrome
60
Q

What renal symptoms can hypercalcaemia cause?

A
  • Polyuria
  • Polydipsia
  • Nephrolithiasis
  • Nephrocalcinosis
  • Distal renal tubular acidosis
  • Nephrogenic diabetes insipidus
  • Acute and chronic renal dysfunction
61
Q

What GIT symptoms can hypercalcaemia cause?

A
  • Anorexia
  • Nausea and vomiting
  • Bowel hypomotility and constipation
  • Pancreatitis
  • Peptic ulcer disease
62
Q

What MSK symptoms can hypercalcaemia cause?

A
  • Muscle weakness
  • Bone pain
  • Osteopenia/osteoporosis
63
Q

What neurological symptoms can hypercalcaemia cause?

A
  • Decreased concentration
  • Fatigue
  • Confusion
  • Stupor, coma
64
Q

What cardiovascular symptoms can hypercalcaemia cause?

A

• Shortening of the QT interval
• Bradycardia
Hypertension

65
Q

What should you enquire about in a hypercalcaemia history?

A
  • Symptoms of hypercalcaemia
  • Systemic enquiry
  • Medications
  • Family history
66
Q

What should you look for on examination of hypercalcaemia?

A
  • Lymph nodes

- Concerns about malignancy (breast, lung, etc.)

67
Q

What investigations should be carried out for hypercalcaemia?

A
  • U+Es
  • Ca
  • PO4
  • Alk phos
  • Myeloma screen
  • Serum ACE
  • PTH
  • Consider ECG
68
Q

What is normally affected by primary hyperparathyroidism?

A
  • F:M 3:1

- Incidence peaks 50-60 years

69
Q

What can cause primary hyperparathyroidism?

A

Most cases are sporadic but has been associated with neck irradiation or prolonged lithium use

  • 85% parathyroid adenoma
    - 15% four gland hyperplasia
  • <1% MEN type 1 or 2A
  • <1% parathyroid carcinoma
70
Q

How do patients with primary hyperparathyroidism present?

A

Most patients are asymptomatic at diagnosis

71
Q

What investigations should be carried out for primary hyperparathyroidism?

A
  • Ca, PTH
  • U+Es: check renal function
  • Abdominal imaging: renal calculi
  • DEX: osteoporosis
  • 24 hour urine collection for calcium: Excl. FHH
  • Vitamin D
  • Parathyroid ultrasound
  • SESTAMIBI
72
Q

What are the indications for surgery in primary hyperparathyroidism?

A

The presence of any of the below features would be an indication for parathyroid surgery

  • Presence of symptoms due to hypercalcaemia
  • Serum calcium >0.25mmol/L above the upper limit of normal (2.85 in Aberdeen)
  • Skeletal: osteoporosis on DEXA or vertebral
  • Renal: eGFR /,60 or presence of kidney stones
  • Age <50 years
73
Q

How can primary hyperparathyroidism be managed medically?

A
  • Generous fluid intake
  • Cinacalcet (acts as calcimetic i.e. mimics effect of calcium on the calcium sensing receptor on chief cells, this leads to a fall in PTH and subsequently calcium levels)
74
Q

What is familial hypocalciuric hypercalcaemia?

A

Autosomal dominant disorder of the calcium sensing receptor

75
Q

How is familial hypocalciuric hypercalcaemia managed?

A

Benign so no therapy indicated

76
Q

What may investigations of familial hypocalciuric hypercalcaemia show?

A
  • PTH normal or slightly elevated
  • No evidence of abnormal parathyroid tissue on ultrasound or isotope scan
  • Positive family history so screen young family members for diagnosis
77
Q

Describe hypercalcaemia caused by: local osteolytic hypercalcaemia

A

Frequency: 20%
Bone metastases: common, extensive
Causal agent: Cytokines, chemokines, PTHrP
Typical tumours: Breast cancer, multiple myeloma, lymphoma

78
Q

Describe hypercalcaemia caused by: humoral hypercalcaemia of malignancy

A

Frequency: 80%
Bone metastases: minimal or absent
Causal agent: PTHrP
Typical tumours: Squamous cell cancer (e.g. head and neck, oesophagus, cervix or lung), renal, ovarian, endometrial & breast cancer

79
Q

Describe hypercalcaemia caused by: 1,25 (OH)2 D-secreting lymphomas

A

Frequency: <1%
Bone metastases: variable Variable
Causal agent: 1,25 (OH)2D
Typical tumours: lymphoma (all types)

80
Q

Describe hypercalcaemia caused by: ectopic hyperparathyroidism

A

Frequency: <1%
Bone metastases: variable
Causal agent: PTH
Typical tumours: variable

81
Q

Describe MEN type 1 in hypercalcaemia

A

Associations

  • Primary hyperparathyroidism
  • Pancreatic
  • Pituitary
  • > 95% MEN 1 will have hyperparathyroidism
  • MENIN mutation (chromosome 11)
  • 2-4% of cases of PHP may be MEN1
  • Usually presents in the 2nd to 4th decade of life
  • Multigland involvement, high recurrence risk
82
Q

Describe MEN type 2A in hypercalcaemia

A

Associations

  • Medullary thyroid cancer
  • Pheochromocytoma
  • Primary hyperparathyroidism
  • RET mutation
  • 20-30% of MEN2A have hyperparathyroidism
  • Usually milder disease than MEN1
83
Q

How should those with hypercalcaemia be managed?

A
  • Rehydration
  • After rehydration, intravenous bisphosphonates
    • Zolendronic acid 4 mg over 15 minutes
    • Give more slowly and consider dose reduction if renal impairment
    • Calcium will reach nadir at 2-4 days
84
Q

Describe rehydration in the treatment of hypercalcaemia

A
  • 0.9% saline 4-6 litres over 24 hours
  • Monitor for fluid overload
  • Consider dialysis if severe renal failure
85
Q

What are the 2nd line treatments in hypercalcaemia?

A
  • Glucocorticoids
  • Calcitonin
  • Calcimimetics
  • Parathyroidectomy
86
Q

When are glucocorticoids used in hypercalcaemia?

A

In lymphoma, other granulomatous disease or 250HD poisoning

87
Q

When is calcitonin used in hypercalcaemia?

A

Can be considered if poor response to bisphosphonates

88
Q

When are calcimimetic used in hypercalcaemia?

A

Licensed for hypercalcemia due to primary hyperparathyroidism, parathyroid carcinoma or renal failure

89
Q

When is a parathyroidectomy used in hyperparathyroidism?

A

Can be considered in acute presentation of primary hyperparathyroidism if severe hypercalcaemia and poor response to other measures

90
Q

What are the low PTH causes of hypothyroidism?

A
  • Genetic disorders
  • Post-surgical (thyroidectomy, parathyroidectomy, radical neck dissection)
  • Autoimmune
  • Infiltration of the parathyroid gland (granulomatous, iron overload, metastases)
  • Radiation-induced destruction of parathyroid glands
  • Hungry bone syndrome (post parathyroidectomy)
  • HIV infection

endocrine system 1 (25 decks)

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