Magnesium

Question 1

What compartments are Mg concentrated in?

Answer 1

Bone 55% and ICF 45%

Question 2

What forms does Mg exist in?

Answer 2

ionised 60%, complexed 15% (to phosphate, citrate or bicarbonate) or protein bound 25%

Question 3

What factor affects the concentration of the different Mg forms?

Answer 3

pH and protein concentration - increased protein binding with increased pH

Question 4

What function does Mg serve?

Answer 4

Cofactor in over 300 enzymatic reactions, e.g. energy metabolism, calcium & potassium channels, membrane stabilisation & neuromuscular excitatability, protein & NA synthesis, oxidative phosphorylation, and the formation &utilisation of ATP

Question 5

What other electrolyte exist at a higher conc than Mg intracellularly?

Answer 5

K+

Question 6

How does the redistribution of Mg occur?

Answer 6

magnesium is absorbed in the GI tract into the ECF and plasma, where it will redistribute to bone, soft tissue and intracellular magnesium or be lost in the form of sweat. Amount absorbed is inversely proportional to the dietary intake

Question 7

What organ can conserve Mg when its low?

Answer 7

The kidney

Question 8

How does Mg reabsorb in the kidney?

Answer 8

Transcellular and paracellular reabsorption

Question 9

Describe transcellular absorption?

Answer 9

Mg leaves the TRPM6 channel, but the release into the blood is unknown

Question 10

Describe paracellular absorption?

Answer 10

Mg2+ absorbed via paracellin-I claudin 19 on the apical membrane.

Question 11

What parts of the nephron absorb Mg?

Answer 11

proximal tubule, thick ascending limb and the distal convoluted tubule

Question 12

What disorder is caused by mutations to the channels associated with renal reabsorption of Mg?

Answer 12

magnesium wasting disorder

e.g.TRPM6 -gisem syndrome

Question 13

How does the state of Mg conc affect PTH secretion?

Answer 13

The release and the action of the PTH is dependent on Mg. The PTH stimulation is stimulated by modest hypomagnesaemia and suppressed in hypermagnesaemia. Furthermore, profound hypomagnesaemia inhibits PTH release

Question 14

What are some symptoms of hypomagnesaemia?

Answer 14

Typically most people will be asymptomatic but can include tetany and seizures (most common), anorexia &nausea, tremor, apathy, depression, agitation, confusion, hypokalaemic, hypocalcaemic

Question 15

How does alcohol consumpyion affect magnesium levels?

Answer 15

causes hypomagnesaemia

Question 16

Why do neuromuscular symptoms occur in hypomagnesaemia?

Answer 16

Volatage gated Ca2+ channels (act to let in Ca2+ to induce neurotransmitter release for muscle contraction) of the presynaptic neuron can be inhibited by magnesium (stabilises exons), but under low magnesium this occurs unregulated. The contraction of muscle become uncontrollable

Question 17

What are some cardiac effects of hypomagnesaemia?

Answer 17

Cause dysrhythmia. The hypomagnesaemia causes decreased activity of ATPase, loss of intracellular K (leak from ICF to ECF) and subsequent urinary loss.
The ratio between intracellular and extracellular leads to increased electrical excitability, causing irregularities in the heartbeat rhythm

Question 18

What needs to be taken into account when treating dysrhythmias?

Answer 18

The therapy for dysrhythmias needs to take magnesium levels into account as hypomagnesemia patients are less responsive.

Question 19

What are the general causes of hypomagnesaemia?

Answer 19

Inadequate intake, malabsorption, intracellular shift, or renal tubular dysfunction

Question 20

Describe inadequate intake of Mg in alcoholics and healthy individuals.

Answer 20

Inadequate intake of magnesium is a typical diagnosis for alcoholics due to greater episodes of vomiting and diarrhoea - as well as eating less

In healthy humans it may be a result of protein calorie malnutrition

Question 21

What is the most common cause of hypomagnesaemia?

Answer 21

Patients in the ICU can commonly develop hypomagnesaemia due to prolonged infusion or ingestion of low Mg diets

Question 22

What disorders of malabsorption cause hypomagnesaemia?

Answer 22

IBD (diarrhoea), gluten enteropathy, intestinal bypass, radiation enteritis, familial primary hypomagnesaemia, or drugs (PPIs – commonly used by GPs).

Question 23

Describe intracellular shifts causing hypomagnesaemia

Answer 23

Refeeding syndrome, hungry bone syndrome, treatment of diabetic ketoacidosis, and acute pancreatitis result in shifts of magnesium from extracellular to intracellular compartments

Question 24

Name some renal tubular dysfunctions causing hypomagnesaemia.

Answer 24

Alcoholism, hyperaldosteronism (increased clearance and excretion), familial magnesuric hypomagnesaemia, Bartters syndrome, post renal obstruction, post-transplant, or osmotic diuresis

Question 25

Name some drugs causing hypoaldosteronism

Answer 25

proton pump inhibitor, nephrotoxic drugs, diuretics

Question 26

How does burns affect Mg status?

Answer 26

Causes hypomagnesaemia

Question 27

How is hypomagnesaemia diagnosed?

Answer 27

Review patients diet, alcohol intake, GI symptoms and drug review.
Clinical assessment is to investigate neuromuscular symptoms or cardiac symptoms (ECG). Blood and urine samples are useful

Question 28

What blood tests are run in hypomagnesaemia?

Answer 28

Can determine Mg, bone profile (calcium/phosphate, vit D, PTH), glucose/HbA1c (DKA), potassium, and TFTs

Allows to understand the presence of an underlying conditions

Question 29

How is the urine sample utilised in hypomagnesaemia investigations?

Answer 29

24hr urine sample is used to calculat the fractional excretion of Mg
Where >2% FE Mg suggest renal Mg wasting e.g. bartters

Question 30

What managements of hypomagneseamia are available?

Answer 30

The magnesium level can be increased using supplement magnaspartate, which is a 6.5g sachet containing magnesium-L-aspartate which is 10mmol of magnesium. Or Mg can be given using a Mg sulphate IV in a litre of 5% dextrose or saline 0.9% over 24hrs

Question 31

What conditions have been shown to be benefitting from Mg supplements?

Answer 31

Acute MI with recurrent ventricular fibrillation, recurrent ventricular tachycardia, complex ventricular tachycardia, or supraventricular tachycardia

Question 32

State the causes of hypermagnesaemia?

Answer 32

Increased intake, intracellular shifts, and renal failure

Question 33

Increased Mg is usually iatrogenic. True or false?

Answer 33

True. Due to oral (generally + CRF), rectal (purgation) or parenterally (pre-eclampsia).

Question 34

Intracellular shifts causing hypermagnesaemia can be seen in what conditions?

Answer 34

Tumour lysis syndrome, haemolysis and acute acidosis

Question 35

How does renal failure cause hyperMg

Answer 35

This means the kidney will fail to excrete Mg appropriately. Can be caused by rhabdomyolosis

Question 36

Match the following Mg conc with symptoms.

1. 2mmol/L
2. 2-3nmol/L
3. 3-5mmol/L
4. > 5mmol/L

A. Nausea, flushing, headaches, diminished reflex tendons
B. Areflexia, ECG changes, somnolence, hypocalcaemia
C. Asymptomatic
D. Respiratory paralysis and cardiac arrest

Answer 36

1C
2A
3B
4D

Question 37

Describe magnesium levels and the effect on synapses?

Answer 37

The neurologic manifestations are the result of the inhibition of acetylcholine release from the neuromuscular endplate due to increased extracellular magnesium levels

In simple hyperMg blocks acetylcholine release, thus blocking the synapses

Question 38

How to treat hyperMg?

Answer 38

Firstly, discontinue a current therapy such as IV administration/Mg supplements.

The approach is dependent on the renal function. Thiazide diuretics can be adminsitered to increase excretion. Patients with advanced CKD require haemodialysis.

IV calcium gluconate can be adminsitered to provide a Mg antagonist

Question 39

How does IV calcium gluconate treat hyperMg?

Answer 39

The rationale is that the actions of magnesium in neuromuscular and cardiac function become antagonized by calcium.