Calcium Disorders

Question 1

Calcium function

Answer 1

Bone mineralization
Blood clotting
Muscle contraction
Nerve function + neurotransmission

Question 2

Serum calcium levels

Answer 2

2.2-2.6 mmol/L

Question 3

Calcium state

Answer 3

Most serum calcium bound to plasma proteins (mainly albumin)
Only unbound calcium is biologically active
Serum calcium always needs to be corrected for albumin concentration

Question 4

Serum calcium + albumin conc

Answer 4

+/- 0.02 mmol/L for every gram that albumin is below/above 40g/dL

Question 5

Calcium hormonal regulation

Answer 5

Vitamin D
Parathyroid hormone
(calcitonin)

Question 6

Vitamin D conversion

Answer 6

Vitamin D3 (cholecalciferol) - synthesizes in sun-exposed epidermis
Requires 2 activation (hydroxylation) steps
Liver- 25 hydroxycholecalciferol (majority Vit D in this form)
Kidney- 1,25-dihydroxycholecalciferol (calcitriol)

Question 7

Majority of Vit D is in this form

Answer 7

25-hydroxycholecalciferol

Question 8

Vit D bound

Answer 8

25-dihydroxycholecalciferol mostly bound to plasma proteins

1,25-dihydroxycholecalciferol largely unbound

Question 9

1,25-dihydroxycholecalciferol half life

Answer 9

Short

15 hours

Question 10

Calcitriol binds to

Answer 10

Nuclear vitamin D receptors

Question 11

Vit D in Gut

Answer 11

Vit D increases the absorption of dietary calcium and phosphate

Question 12

Vit D in kidney

Answer 12

Increases calcium and phosphate reabsorption

Question 13

Vit D in bone

Answer 13

Stimulates osteoclasts to release calcium and phosphate

Question 14

Parathyroid gland

Answer 14

4 parathyroid glands

Question 15

PTH

Answer 15

Secreted by chief cells within parathyroid gland
Released in response to low calcium levels
Can also be stimulated by changes in phosphate concentration
Acts to increase serum Ca

Question 16

PTH on Kidney

Answer 16

Increases Vit D
Increases Ca and Hydrogen reabsorption
Decreases phosphate and bicarbonate reabsorption

Question 17

PTH on bone

Answer 17

Inhibits osteoblasts

Stimulates osteoclasts

Question 18

Parathyroid-related peptide (PTHrP)

Answer 18

Acts via same cell surface receptor as PTH

Synthesised by placenta + breast, where it contributes to 1 alpha hydroxylation

Question 19

Calcitonin

Answer 19

Secreted by parafollicular C cells of thyroid
In response to raised serum calcium
Acts on renal tubules to reduce calcium and phosphate reabsorption
Inhibits osteoclasts

Question 20

Hypocalcaemia signs and symptoms

Answer 20

Muscle cramps
Trousseau’s sign- carpopedal spasm when applying BP cuff
Tetany and neuromuscular excitability
Chvostek’s sign- tapping over the facial nerve causes facial muscles to twitch
Mood swings
Convulsions
Cardiac arrhythmias

Question 21

Hypocalcaemia causes- hypoparathyroidism

Answer 21

Surgical removal (thyroidectomy)
Autoimmune damage
Congenital (De George Syndrome agenesis of the parathyroid)

Question 22

Hypocalcaemia causes- not hypoparathyroidism

Answer 22

Hypomagnesaemia
Renal failure (PTH can no longer increase Vit D hydroxylation, and hypocalcaemia can develop)
PTH resistance (aka pseudohypoparathyroidism)

Question 23

Hypocalcaemia treatment

Answer 23

Oral calcium

Calcitriol

Question 24

Hypercalcaemia signs and symptoms

Answer 24

Tiredness + fatigue
Anorexia + nausea
Thirst + polyuria
Muscle weakness
Headache
Body pain
Renal stones
Abdo pain (constipation, pancreatitis)
Mood disturbance 
Cardiac arrhythmias

Question 25

Hypercalcaemia causes

Answer 25

``` Primary hyperparathyroidism Malignancy Drugs and diet Familial benign hypercalcaemia Granulomatous disease- Sarcoidosis Tertiary hyperparathyroidism ```

Question 26

Primary hyperparathyroidism

Answer 26

Relatively common 80% single parathyroid adenoma (remainder hypertrophy of more than one gland) Parathyroid malignancy rare

Question 27

If parathyroid malignancy found in patients <45, consider..

Answer 27

MEN syndrome

Question 28

Hypercalcaemia- malignancy that secretes PTHrP

Answer 28

Classically squamous lung cell cancer

Question 29

Hypercalcaemia- malignancy

Answer 29

Malignancy that secretes PTHrP Bone metastases Multiple myeloma- sclerotic bone lesions

Question 30

Hypercalcaemia- secondary hyperparathyroidism

Answer 30

Usually in renal failure context Lack activation of Vit D, with hypocalcaemia, as well as increased phosphate levels stimulate the parathyroid gland to increase production to compensate

Question 31

Hypercalcaemia- tertiary hyperparathyroidism

Answer 31

With prolonged secretion of parathyroid hormone, the glands may become autonomous Over secrete PTH even when calcium levels have normalised

Question 32

Hypercalcaemia causes- drugs and diets

Answer 32

Thiazide diuretics - increased calcium reabsorption from distal tubule Vit D overdose

Question 33

Hypercalcamia Causes- familial benign hypercalcaemia

Answer 33

``` AKA familial hypocalciuric hypercalcaemia (FHH) Autosomal dominant Defective calcium receptor on PT gland Leads to reduce negative feedback --> elevated PTH and calcium Elevated PTH causes hypocalciuria FHH doesn't need treatment ```

Question 34

Hypercalcamia causes- sarcoid and GH

Answer 34

Non-caseating granulomas can have 1 alpha hydroxylase activity GH can also stimulate renal alpha 1 hydroxylase activity

Question 35

Hypercalcaemia investigations

Answer 35

Serum Ca and phosphate PTH- primary, tertiary or FHH: high or inappropriately "normal" in context of elevated calcium Vit D (PTH raised in Vit D deficiency) 24 hr urinary Ca collection

Question 36

Hypercalcaemia investigations- primary hyperparathyroidism

Answer 36

Imaging of parathyroid- CT or MRI, isotope uptake scan | Venous sampling

Question 37

Hypercalcaemia investigations- other

Answer 37

Look for malignancy- XR chest, CT Urinary Bence Jones proteins Serum ACE

Question 38

Hypercalcaemia treatment- Severe

Answer 38

EMERGENCY IV rehydration IV biphosphonates (e.g. pamidronate) Steroids in haematological malignancy or sarcoidosis

Question 39

Hypercalcaemia treatment- mild

Answer 39

Can monitor as rarely worsens

Question 40

Hypercalcaemia- surgery

Answer 40

Considered when complications: Renal impairment Stones Bone demineralisation