Clinical Aspects of Calcium Homeostasis Flashcards by Annie Caldwell

Sources of calcium

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

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Functions of calcium

Bone formation
Cell division and growth
Muscle contraction
Neurotransmitter disease

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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)

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Normal range of plasma calcium

2.20 - 2.60 mmol/l

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Acidosis and calcium

Acidosis increases ionised calcium thus predisposing to hypercalcaemia

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Sources of vitamin D

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

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

Via calcium sensing receptor (CSR)

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An increase in Ca2+ does what to PTH levels?

Decreases

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

An increase

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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

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What serum calcium is classed as hypocalcaemia?

< 2.20

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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

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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

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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)

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Causes of secondary hyperparathyroidism in response to hypocalcaemia

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

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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

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Investigations for hypocalcaemia

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

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When does pseudohypoparathyroidism present?

Childhood

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Definition of pseudohypoparathyroidism

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

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Blood levels of pseudohypoparathyroidism

Hypocalcaemia
Hyperphosphatemia
Elevated PTH concentrations

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What condition can occur in patients with pseudohypoparathyroidism?

Albright’s Hereditary Osteodystrophy (AHO)

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Presentation of Albright’s Hereditary Osteodystrophy (AHO)

Obesity
Short stature
Shortening of metacarpal bones

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What is pseudo-pseudoparahypothyroidism

AHO alone without abnormalities of calcium or parathyroid hormone

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Treatment of “mild” hypocalcaemia

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

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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