Calcium Pathophysiology and Clinical Aspects - Hypocalcaemia

Question 1

Name dietary sources of calcium

Answer 1

• Milk, cheese and other dairy foods
• Green leafy vegetables - broccoli, cabbage and okra
• Tofu
• Soya beans
• Nuts

Question 2

Name four functions of calcium

Answer 2

• Bone formation
• Cell division and growth
• Muscle contraction
• Neurotransmitter release

Question 3

Name four different pathways of calcium metabolism?

Answer 3

• Secretion and absorption into gut lumen and excrete via faeces
• Filtration and reabsorption by the kidneys
• Absorption and deposition into bone (98% of calcium)
• Diffusion into and out od cells

Question 4

How is calcium stored in the bone?

Answer 4

Inactive form of calcium

Question 5

What proportion of calcium is bound in plasma?

Answer 5

• 45% bound (mainly to albumin)
• 10% non-ionised or complexed to citrate, PO4 et
• 45% ionised

Question 6

What is most of the plasma calcium bound to?

Answer 6

Albumin

Question 7

How much calcium is found in the plasma?

Answer 7

2.2-2.6mmol/l

Question 8

How is free calcium calculated?

Answer 8

• Increased albumin decreases free calcium

* Decreased albumin increases free calcium

Question 9

How does acidosis affect Ca levels?

Answer 9

Increased ionised calcium thus predisposing hypercalcaemia

Question 10

How do you work out corrected calcium?

Answer 10

Adjust Ca by 0.1mmol/l for each 5g/l reduction in albumin from 40g/l

Question 11

Name sources of vitamin D

Answer 11

• Mostly from sunlight
• Small number of food:
- Oily fish (salmon, sardine and mackerel)
- Eggs
- Fortified fat spreads and breakfast cereals

Question 12

Name the different groups at risk of vitamin D deficiency

Answer 12

• Institutionalised patients and prisoners who don’t get outside much
• Pregnancy requires extra vit D
• Children
• Darker skin absorbs less Vit D
• Clothes covering large proportion of body

Question 13

How is the release of parathyroid hormone stimulated?

Answer 13

• Parathyroid chief cells secrete PTH
• Chief cells respond directly changing to Ca concentrations
• Alterations in ECF Ca levels are transmitted into the parathyroid cells via calcium-sensing receptor (CaSR)
• PTH is secreted in response to a fall in calcium

Question 14

What is the relationship between Ca levels and PTH levels?

Answer 14

↑ Ca –> ↓ PTH

↓ Ca –> ↑ PTH

Question 15

What are the actions of parathyroid hormone?

Answer 15

• PTH has direct effects that promote reabsorption of Ca from renal tubules and bone
• PTH mediates the conversion of vitamin D from its inactive to active form in the kidneys

Question 16

What bone problem is caused by lengthy exposures to inappropriate levels of PTH?

Answer 16

Osteoporosis

Question 17

Describe the step of vitamin D metabolism?

Answer 17

1. Vitamin D from sun or food
2. Liver produces inactive Vit D
3. Kidney activates Vit D - this step has input from PTH
4. Active Vit D helps absorb Ca from the gut

Question 18

What are the boundaries of hypocalcaemia?

Answer 18

Serum calcium < 2.2mmol/L

Question 19

What are the clinical features of acute hypocalcaemia?

Answer 19

• Neuromuscular irritability (tetany)
• Paresthesia
• Muscle twitching
• Carpopedal spasm
• Trosseau’s sign

Cardiac:
• Hypotension 
• HF 
• Papilloedema
• Arrythmia

Question 20

What are the clinical features of chronic hypocalcaemia?

Answer 20

• Parkinsonism
• Dementia
• Abnormal dentition
• Dry skin

Question 21

When do symptoms of hypocalcaemia typically present?

Answer 21

Serum calcium falls below 1.9mmol/L

People usually in 2.2mmol/L usually asymptomatic

Question 22

Name different causes of hypocalcaemia

Answer 22

• Hypoparathyroidism - disruption of parathyroid gland due to total thyroidectomy - may be temporary or permanent
• Selective parathyroidectomy
• Severe vit D deficiency
• Mg deficiency
• Cytotoxic drug-induced hypocalcaemia
• Pancreatitis, rhabdomyolysis and large vol. blood transfusions

Question 23

What drug causes Mg deficiency?

Answer 23

Proton pump inhibitors

Question 24

What are the causes of hypocalcaemia which presents with hypoparathyroidism (low PTH)?

Answer 24

• Genetic disorders
• Post-surgical (thyroidectomy, parathyroidectomy)
• Autoimmune
• Infiltration of gland (iron overload, metastases)
• Radiation destruction
• HIV

Question 25

What are the causes of hypocalcaemia which presents with hyperparathyroidism (high PTH)?

Answer 25

* Vit D * Pseudohypoparathyroidism * Hypomagnesia * Renal disease * Acute pancreatitis

Question 26

What drugs cause hypocalcaemia?

Answer 26

* Inhibitors of bone resorption (bisphosphonates) | * Cinacalet

Question 27

What do you need to know in the history and examinations of hypocalcaemia?

Answer 27

``` History: • Symptoms • Ca and Vit D intake • Neck surgery • Autoimmune disorders (can be autoimmune destruction of parathyroid glands -> hypoparathyroidism) • Medication • FH of hypoparathyroidism ``` Exam: • Neck scars

Question 28

What are the investigations used for hypocalcaemia?

Answer 28

* ECG * Serum calcium * Albumin * Phosphate * PTH * U+Es * Vitamin D * Magnesium

Question 29

What is the first investigation carried out when hypocalcaemia in confirmed?

Answer 29

Check PTH | • Different route of investigations depending on if PTH is high or low

Question 30

What is the investigation route for hypocalcaemia if PTH is low?

Answer 30

Check magnesium • Low --> Mg deficiency • Normal --> hypoparathyroidism or calcium sensing receptor defect (rare)

Question 31

What is the investigation route for hypocalcaemia if PTH is high?

Answer 31

``` Check urea and creatinine 1. High -> renal failure 2. Normal --> check for Vitamin D • Low -> Vit D deficiency • Pseudohypoparathyroidism or calcium deficiency ```

Question 32

What does hypoparathyroidism result from?

Answer 32

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

Question 33

What is pseudohypoparathyroidism?

Answer 33

Heterogeneous disorders defined by target organ (kidney and bone) unresponsiveness to PTH Characterised by hypocalcemia, hyperphosphatemia and, in contrast to hypoparathyroidism, elevated rather than reduced PTH concentrations

Question 34

What are the features of pseudohypoparathyroidism?

Answer 34

Albright’s heriditary Osteodystrophy (AHO): Obesity, short stature, shortening of the metacarpal bones that can occur in some patients with Pseudohypoparathyroidism

Question 35

What is the treat of hypocalcaemia > 1.9mmol/L but < 2.2mmol/L?

Answer 35

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

Question 36

What is the treatment of hypocalcaemia < 1.9mmol/L?

Answer 36

* Medical emergency * IV calcium gluconate * Initial bolus (10% calcium gluconate in 5% dextrose IV over 10mins with ECG monitoring) * Calcium gluconate infusion * Treat the underlying cause

Question 37

What is given as Vitamin D replacement and when is it required?

Answer 37

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