Hyper/hypocalcaemia Flashcards

1
Q

What is normal range for calcium?

A

2.2-2.6 mmol/L

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2
Q

What are causes of hypocalcaemia with increased PO43-?

A
  • CKD
  • Hypoparathyroidism
  • Pseudohypoparathyroidism
  • Acute rhabdomyolysis
  • Hypomagnasemia
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3
Q

What are causes of hypocalcaemia with high PTH (secondary hyperparathyroidism)?

A

Secondary hyperparathyroidism in response to hypocalcaemia

  • Vit D deficiency
  • Pseudohypoparathyroidism
  • Hypomagnasemia
  • Renal disease
  • Tumour lysis syndrome
  • Acute pancreatitis
  • Acute respiratory alkalosis
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4
Q

What are causes of hypocalcaemia with low PTH?

A

Parathyroid dysfunction (primary/secondary)

  • Destruction of parathyroid glands - Surgery, autoimmune, radiation, infiltration (iron, copper, tumour)
  • Developmental parathyroid disorders - Isolated hypoparathyroidism, Autosomal recessive, autosomal dominant, or X-linked, Syndromes of hypoparathyroidism associated with complex developmental anomalies (e.g., DiGeorge sequence
  • Hungry bone disease following parathyroidectomy.
  • HIV infection
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5
Q

What is primary hypoparathyroidism?

A

Dysfunction of parathyroid gland - results in low PTH and low Ca2+ - hypocalcaemia

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6
Q

What are causes of primary hypoparathyroidism?

A
  • Autoimmune hypoparathyroidism
  • Congenital hypoparathyroidism
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7
Q

Why can hyperphosphataemia occur in primary hypoparathyroidism?

A

Hyperphosphataemia results from the lack of PTH action on renal phosphate transport to clear phosphate via the kidney - leads to phosphate accumulation

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8
Q

What are causes of secondary hypoparathyroidism?

A
  • Radiation
  • Surgery - thyroidectomy, parathyroidectomy
  • Hypomagnesaemia
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9
Q

What is secondary hypoparathyroidism?

A

In secondary hypoparathyroidism, parathyroid gland dysfunction is the consequence of a primary problem elsewhere, typically sepsis or hypomagnesemia.

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10
Q

What are causes of hypocalcaemia with normal or decreased PO43-?

A
  • Vitamin D deficiency
  • Osteomalacia (increased ALP)
  • Acute pancreatitis
  • Overhydration
  • Respiratory alkalosis
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11
Q

What are features of hypocalcaemia?

A
  • Spasms - carpopedal spasm
  • Perioral paraesthesiae
  • Anxious, irritable, irrational
  • Seizures
  • Muscle tone increase in smooth muscle
  • Orientation impaired + confusion
  • Dermatitis
  • Impetigo herpatiformis
  • Chvostek’s signs, cataracts, chroeoathetosis, cardiomyopathy
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12
Q

What is Chvotsek’s sign?

A

Tapping on the patient’s cheek at a point anterior to the ear and just below the zygomatic bone to stimulate the facial nerve results in twitching of the ipsilateral facial muscles. It is suggestive of latent tetany and increased neuromuscular excitability

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14
Q

What is thought to be the mechnism of Chovtsek’s Sign in hypocalcaemia?

A

Increased neuronal excitability

Calcium is needed to maintain normal neuronal membrane permeability by acting on and blocking sodium channels on the neuronal membrane. If extracellular calcium is low and/or not available, the sodium channels are more permeable. As more sodium enters the cell, the cell becomes less polarised and is more easily stimulated to reach action potential

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15
Q

What is trousseau’s sign?

A

After inflating a cuff above the patient’s systolic blood pressure and leaving it inflated for 3 minutes, muscular contraction – including flexion of the wrist and MCP joints, hyperextension of the fingers and flexion of the thumb on the palm – occurs

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16
Q

How does respiratory alkalosis cause Chovstek’s Sign?

A

Respiratory alkalosis and hyperventilation result in less active ionised calcium – as opposed to total calcium. It is the decrease in ionised calcium that causes increased excitability

When the pH is high (alkalotic), more calcium binds to proteins, making less active calcium available in the extracellular fluid for regular processes, such as blocking sodium channels and maintaining membrane stability

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18
Q

What is thought to be the mechanism behind Trousseau’s sign?

A

Similar mechanism to Chvostek’s sign

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19
Q

In hypocalcaemia, what are symptoms of increased smooth muscle tone in hypocalcemia?

A
  • Colic
  • Wheeze
  • Dysphagia
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20
Q

What cardiac problems can manifest in hypocalcaemia?

A
  • Prolonged QT
  • Hypotension
  • HF
  • Arrythmias
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21
Q

What are features of chronic hypocalcaemia?

A
  • Ectopic Calcification (basal ganglia)
  • Extrapyramidal signs
  • Parkinsonism
  • Dementia
  • Subcapular cataracts
  • Abnormal dentition
  • Dry Skin
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22
Q

If someone had hypocalcaemia, what test would you want to look at?

A

PTH

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23
Q

If someone had hypocalcaemia with low/normal PTH, what would you check?

A

Magnesium

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24
Q

If someone had hypocalcaemia, with low PTH, and low magnesium, what might be the cause of hypocalcaemia?

A

Magnesium defciiency

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25
Q

What might hypocalcaemia with low/normal PTH and normal magnesium suggest as the cause of hypocalcaemia?

A

Hypoparathyroidism or calcium sensing receptor defect

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26
Q

What might you do if you investigated PTH in someone with hypocalcaemia and the PTH was high?

A

Check U+E’s

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27
Q

What might hypocalcaemia with high PTH and high urea and creatinine suggest as the cause of hypocalcaemia?

A

Renal failure

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28
Q

What investigation might you do in someone with hypocalcaemia with high PTH and normal U+E’s?

A

Check vitamin D

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29
Q

What might cause hypocalcaemia with high PTH, normal U+E’s, and low vitamin D?

A

Vitamin D deficiency

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30
Q

What might cause hypocalcaemia with increased PTH with normal U+E’s and normal Vitamin D?

A

Pseudohypoparathyroidism or calcium deficiency

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31
Q

What might you see on investigation of the following in someone with hypocalcaemia caused by Vitamin D deficiency:

  • Total calcium
  • Ionised calcium
  • Phosphate
  • PTH
A
  • Total calcium - low
  • Ionised calcium - low
  • Phosphate - low
  • PTH - High
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32
Q

What might you see on investigation of the following in someone with hypocalcaemia caused by Hypoparathyroidism:

  • Total calcium
  • Ionised calcium
  • Phosphate
  • PTH
A
  • Total calcium - low
  • Ionised calcium - low
  • Phosphate - High
  • PTH - low
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33
Q

What might you see on investigation of the following in someone with hypocalcaemia caused by CKD:

  • Total calcium
  • Ionised calcium
  • Phosphate
  • PTH
A
  • Total calcium - low
  • Ionised calcium - low
  • Phosphate - High
  • PTH - High
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34
Q

What might you see on investigation of the following in someone with hypocalcaemia caused by Respiratory alkalosis:

  • Total calcium
  • Ionised calcium
  • Phosphate
  • PTH
A
  • Total calcium - normal
  • Ionised calcium - low
  • Phosphate - normal
  • PTH - normal/high
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35
Q

What investigations would you consider doing in someone with hypocalcaemia?

A
  • Bedside - ECG, Urinalysis
  • Bloods - Serum total calcium, serum albumin, phosphate, PTH, U+E’s, Vit D, Magnesium, Amylase, CK
  • Imaging - Consider X-ray
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36
Q

What might you see on investigation of the following in someone with hypocalcaemia caused by Respiratory alkalosis:

  • Total calcium
  • Ionised calcium
  • Phosphate
  • PTH
A
  • Total calcium - normal
  • Ionised calcium - low
  • Phosphate - normal
  • PTH - normal/high
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37
Q

What might you see on investigation of the following in someone with hypocalcaemia caused by Acute pancreatitis:

  • Total calcium
  • Ionised calcium
  • Phosphate
  • PTH
A
  • Total calcium - low
  • Ionised calcium - low
  • Phosphate - normal/low
  • PTH - high
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38
Q

What might you see on investigation of the following in someone with hypocalcaemia caused by hypomagnesaemia:

  • Total calcium
  • Ionised calcium
  • Phosphate
  • PTH
A
  • Total calcium - low
  • Ionised calcium - low
  • Phosphate - variable
  • PTH - low/normal
39
Q

How would you manage mild hypocalcaemia?

A
  • Oral Ca2+ tablets
  • If vit D deficient - alfacaldicol
  • If low Mg2+ - Mg2+ supplementation
40
Q

How would you manage severe hypocalcaemia?

A

Medical emergency

  • ABCDE
  • IV calcium gluconate bolus(es), the infusion
  • Treat underlying cause e.g. resp alkalosis, hypomagnasaemia
41
Q

What might you see on ECG in someone with hypocalcaemia?

A
  • Long QT interval
  • Arrythmias
55
Q

Why do those with CKD have increased phosphate and PTH?

A

Due to impaired phosphate clearence and secondary hyperparathyroidism

61
Q

What rate would you give an IV calcium gluconate bolus in someone with severe hypocalcaemia?

A

10–20 mL 10% calcium gluconate in 50–100 mL of 5% dextrose i.v. over 10 min with ECG monitoring.

This can be repeated until the patient is asymptomatic.

62
Q

What rate and concentration of calcium gluconate infusion would you give someone being treated for hypocalcaemia following IV calcium gluconate bolus?

A

Dilute 100 mL of 10% calcium gluconate (10 vials) in 1 L of Normal saline or 5% dextrose and infuse at 50–100 mL/h.

Titrate the rate of infusion to achieve normocalcaemia and continue until treatment of the underlying cause has taken effect

63
Q

How would you manage hypoparathyroidism?

A
  • Ca2+ supplements
  • Calcitriol supplements
64
Q

If you had confirmed hypercalcaemia, what investigation would you want to do to determine the cause?

A

Check corrected calcium and PTH

65
Q

IF someone had hypercalcaemia with a raised/normal PTH, what might you think of as the cause of the hypercalcaemia?

A
  • Primary hyperparathyroidism
  • Familial hypocalciuric hypercalcaemia
  • Tertiary hyperparathyroidism
66
Q

What is pseudohypoparathyroidism?

A

Failure of target cells to respond to PTH

67
Q

If someone had hypercalcaemia with a low PTH, what might this suggest about the cause of the hypercalcaemia?

A

Caused by malignancy or drugs

68
Q

What are features of pseudohypoparathyroidism?

A
  • Short metacarpals (esp 4th and 5th)
  • Round face
  • Short stature
  • Calcified basal ganglia
69
Q

What is pseudo-pseudohypoparathyroidism?

A

Describes the phenotypic defect of pseudohypothyroidism but without any abnormalities for calcium metabolism

70
Q

What drugs can cause hypocalcaemia?

A
  • Bisphosophonates
  • Calcitonin
  • Phenytoin
  • Calcium chelators - EDTA, citrate, phosphate
  • Foscarnet
71
Q

What are parathyroid mediated causes of hypercalcaemia?

A
  • Primary hyperparathyroidism
  • MEN syndromes
  • Familial isolated hyperparathyroidism
  • Familial hypocalciuric hypercalcaemia
  • Tertiary hyperparathyroidism (renal failure)
72
Q

What are non-parathyroid mediated causes of hypercalcaemia?

A
  • Hypercalcaemia of malignancy
  • Vit D intoxication
  • Granulomatous disorders - Sarcoidosis, TB, Berylliosis, Histioplasmosis, Wegener’s
73
Q

If someone had hypercalcaemia with raised albumin and raised urea, what might be the cause of their hypercalcaemia?

A

Dehydration

74
Q

What are medications that cause hypercalcaemia?

A
  • Thiazide diuretics
  • Lithium
  • Teriparatide
  • Excessive vitamin A
  • Theophylline toxicity
75
Q

If someone had hypercalcaemia with normal/low albumin and low phosphate and normal urea, what might be the cause of their hypercalcaemia?

A

Primary or tertiary hyperparathyroidism

76
Q

If someone had hypercalcaemia with normal/low albumin and normal or raised phosphate and raised ALP, what might be the cause of their hypercalcaemia?

A

Increased bone turnover:

  • Bone mets
  • Sarcoidosis
  • Thyrotoxicosis
  • Lithium
77
Q

If someone had hypercalcaemia with normal/low albumin and normal or raised phosphate and normal ALP, what might be the cause of their hypercalcaemia?

A

Increased bone turnover:

  • Myeloma
  • Vit D excess
  • Sarcoidosis
  • Milk-alkali syndrome
78
Q

How would you manage hypercalcaemia?

A

If Ca2+ > 3.5 mmol/L and symptomatic:

  • ABCDE
  • Monitor with ECG
  • Correct dehydration - IV 0.9% saline
  • Bisphosphonates - IV Zolendronic acid 4mg over 15 mins
  • If bisphosphonates not working - 2nd line therapy
  • Consider treating cause - chemotherapy, steroids, calcimimetics etc.
79
Q

What are endocrine causes fo hypercalcaemia?

A
  • Hyperparathyroidism
  • Hyperthyroidism
  • Acromegaly
  • Phaeochromocytoma
  • Adrenal insufficiency
80
Q

What is primary hyperparathyroidism?

A

A disorder of one or more of the parathyroid glands (figure 1). The parathyroid gland(s) becomes overactive and secretes excess amounts of parathyroid hormone (PTH)

81
Q

What are causes of primary hyperparathyroidism?

A
  • Solitary adenoma
  • Hyperplasia of all glands
  • Parathyroid cancer
  • MEN 1/2A
82
Q

What is secondary hyperparathyroidism?

A

Refers to the excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels) and associated hyperplasia of the glands.

83
Q

How would you manage primary hyperparathyroidism?

A

Non-surgical

  • Advise increased fluid intake
  • Avoid thiazides, high Ca2+ and Vit D intake
  • Calcimimetic drugs - cincalcet

Surgical

  • Excision of hyperparathyroid adenoma/all four hyperplastic glands
84
Q

What options would you consider as second line therapy for treating severe hypercalcaemia if response to bisphosphonate bolus had an inadequate response?

A
  • Calcitonin
  • Prednisolone - excess 1, 25 vit d production
  • Cinacalcet - primary hyperparathyroid, parathyroid carcinoma, renal failure
  • Dialysis - refractory hypercalcaemia, severe renal failure
  • Consider Parathyroidectomy - refractory primary hyperparathyroidism
85
Q

What is the most common cause of secondary hyperparathyroidism?

A

Chronic renal failure

86
Q

What are indications for surgery in primary hyperparathyroidism?

A
  • Calcium >2.85 mmol/L
  • Renal calculi
  • Severe symptoms
87
Q

What investigations would you consider doing in someone with suspected primary hyperparathyroidism?

A
  • Bloods - Ca2+, phosphate, U+E’s, Vit D, PTH, ALP
  • Imaging - US kidneys, US neck, SPECT CT/MRI, X-ray hands
88
Q

What is tertiary hyperparathyroidism?

A

Occurs after prolonged secondary hyperparathyroidism, causing the gland to act autonomously having undergone hyperplastic/adenomatous change. This causes increased Ca2+ due to unlimited secretion of PTH.

89
Q

What is the most common cause of tertiary hyperparathroidism?

A

Chronic renal failure

90
Q

What is malignant hyperparathyroidism?

A

Parathryoid-related protein (PTHrP) is produced by some squamous cell lung cancers, breast and renal cell carcinomas. This mimics PTH resulting in increased Ca2+

91
Q

What happens to PTH levels in malignant hyperparathyroidism?

A

Decreases due to increased action of PTHrP

92
Q

What are features of hypercalcaemia?

A

Bones, stones, groans and psychic moans

  • GI - anorexia,/weight loss, nausea & vomiting, constipation, abdominal pain, pancreatitis
  • Renal - polyuria, polydipsia, calculi, distal renal tubular acidosis, nephrogenic DI
  • MSK - bone pain, muscle weakness, fractures
  • Neuro - decreased concentration, confusion, fatigue, stupor/coma
  • CVS - shortened QT, bradycardia, hypertension, cardiac arrest
  • Systemic - ectopic calcification
93
Q

What investigations would you consider doing in someone with suspected hypercalcaemia?

A
  • Bedside - ECG
  • Bloods - FBC, U&Es, Ca, PO4, Alk phos, Myeloma screen, Serum ACE, PTH, Vit D
  • Imaging - Abdo USS, DEXA, Isotope Bone scan,
  • Other - 24 hr urinary calcium
94
Q

What is corrected calcium?

A

Corrected calcium concentration estimates the total concentration as if the albumin concentration was normal - usually taken as 40 g/l. A typical correction is that for every 1 g/l that the albumin concentration is below this mean, the calcium concentration is 0.02 mmol/l below what it would be if the albumin concentration was normal; i.e.

Corrected [Ca] = measured [Ca] + {(40 - [albumin]) * 0.02}

95
Q

How is hypercalcaemia associated with malignancy?

A
  • Osteolytic lesions from bony mets
  • Tumours releasing PTHrP acting on PTH receptors
98
Q

What would you do a 24 hour urine calcium for in someone who is hypercalcaemic?

A

Look for familial hypercalciuric hypercalcaemia

100
Q

What might indicate malignancy as a cause of hypercalcaemia in the following investigations:

  • Albumin
  • Cl-
  • K+
  • PO43-
  • ALP
A
  • Decreased albumin
  • Decreased chloride
  • Decreased K+
  • Increased PO43-
  • Increased ALP
101
Q

What sex does primary hyperparathyoridism most commonly occur in?

A

Females

102
Q

What is familial hypercalciuric hypercalcaemia?

A

Autosomal dominant disorder of the calcium sensing receptor

103
Q

What is ectopic calcification?

A

Ectopic calcification is a pathologic deposition of calcium salts in tissues or bone growth in soft tissues.

104
Q

What are causes of ectopic calcification?

A
  • PTH and other causes of hypercalcaemia
  • Amyloidosis
  • Renal failure
  • Addison’s disease
  • TB nodes
  • Toxoplasmosis
  • Histioplasmosis
  • Overdose of Vit D
  • Raynaud’s associated disease - SLE, systemic scleerosis
  • Muscle primaries/leiomyosarcoma
  • Ossifying mets/ovarian mets
  • Nephrocalcinosis
  • Endocrine tumours
111
Q

What risks are associated with a plasma calcium >3.5 mmol/L?

A

Arrythmias and coma

112
Q

What are the main features of primary hyperparathyroidism?

A
  • Hypertension
  • Features of hypercalcaemia
  • Features of bone resorption - pain, osteoporosis etc.
113
Q

What multiple endocrine disorder is priamry hyperparathyroidism associated with?

A

MEN-1

114
Q

What might you see on imaging in someone with priamry hyperparathyroidism?

A
  • Osteotitis fibrosa cystica
  • Pepper pot skull
  • Acro-osteolysis
117
Q

What ECG findings might you have in hypercalcaemia?

A

Shortened QT

120
Q

How does hyperphosphataemia cause hypocalcaemia?

A

High phosphate increases binding of free calcium

121
Q

What mnemonic can you use to think of differentials for hypercalcaemia?

A

VITAMIN TRAPS

  • Vitamin A and D excess
  • Immobilisation
  • Thyrotoxicosis
  • Addison’s/Acidosis
  • Milk-alkali syndrome
  • Inflammatory disorders
  • Neoplastic disease
  • Thiazides
  • Rhabdomyolysis
  • AIDs
  • Paget’s, Parathyroid disease, parenteral nutrition
  • Sarcoidosis