Renal physiology - magnesium and potassium - De Zoysa

Question 1

Magnesium

Answer 1

cation, essential for human function

total magnesium content of the human body is ~20mmol/Kg of fat free tissue

Question 2

Distribution of Mg

Answer 2

99% found in bone (hydroxyapatite), muscle and soft tissue
Intracellular Mg ranges from 5 to 20mmol/L
Extracellular Mg accounts for 1%

Question 3

Magnesium in physiology

Answer 3

Bone formation 
Co-factor in > 300 enzymatic reactions 
- ATP metabolism 
- Muscle contraction and relaxation 
- normal neurologic function 
- release of neurotransmitters 
Regulation of vascular tone 
Cardiac rhythm 
Platelet activated thrombosis

Question 4

Why is it so hard for Mg to travel into cells?

Answer 4

is always surrounded by heaps of water molecules when in our body, so hard to slip through intracellular channels, so there need to be active processes that strip the water molecules from around the ion

Question 5

What is normal magnesium homeostasis?

Answer 5

A lot comes from the daily diet, some of this will come from water but this depends on how water is processed
about 100mg excreted through the kidneys each day

Question 6

Mg reabsorption throughout the nephron

Answer 6

10-20% in PCT (paracellular channel, need Na/KATPase pump)
10% DCT (transcellularly)
60-70% thick ascending limb of the LoH (paracellular through claudin proteins, mutations here can cause low Mg)

In contrast to sodium and calcium reabsorption, a lot of which occurs in the PCT

Question 7

Assessment of Mg

Answer 7

serum Mg 
Red cell Mg 
24 hour excretion 
Oral Mg retention test, supplemented by IV retention test 
Isotope analysis

Question 8

Causes of hypomagnesamia

Answer 8

1. Decreased dietary intake
2. GI malabsorption and loss
3. Endocrine - hyperaldosteronism, DM, SIADH, “hungry bone syndrome
4. Renal loss
   - congenital
   - Acquired
   - Drug induced

Question 9

Example of drugs that can cause tubular dysfunction –> hypomagnesamia

Answer 9

Amino glycosides
Amphoteriicin B
Cisplatin
Proton pump inhibitors (e.g. omeprazole)

Question 10

Symptoms of hypomagnesaemia

Answer 10

Weakness and fatigue 
Fasciculations/cramps 
tetany/carpopedal spasm 
Numbness / parasthesia 
Seizures 
Arrhythmias

Question 11

treatment?

Answer 11

IV magnesium (magnesium sulphate) 
oral used in most cases

Question 12

Hypermagnesemia

Answer 12

in advanced CKD the compensatory mechanisms start to become inadequate
excessive oral admin of magnesium salts or magnesium containing drugs
Iatrogenic

Question 13

Potassium

Answer 13

Majority inside cells (a little bit i the skeleton and ECF)

Question 14

Potassium haemostasis

Answer 14

daily oral intake 1560-5850mg/day

At healthy steady state 90-95% excreted in urine, 5-10% excreted in faeces

Question 15

Internal balance

• What maintains K+ levels
• Initial changes in extracellular K+ buffered by?

Answer 15

• kidneys

- movement of K into or out of skeletal muscle, regulated by insulin and catecholamines

Question 16

hyper glycaemia will cause?

Answer 16

K efflux from cell

Question 17

K reabsorption in nephron

Answer 17

60% in PCT (paracellular, in association with NaKATPase )
30% in thick ascending (active with NaKCl channel and ROMK channel)
Variable in DCT and CD (where regulation occurs: aldosterone and angiotensin)

Question 18

hypokalemia

Answer 18

serum K <3.5mmol/L 
Symptoms 
- muscle weakness 
- Paralysis 
- cardiac conduction abnormalities 
- Cramps 
- constipation

Question 19

Hypokalemic periodic paralysis

Answer 19

autosomal dominant (rare) or thyrotoxic 
Abnormal K+ channels on cell membrane 
Tigger is often high carb meal (insulin) or SNS activation (beta agonist)anxiety or exercise 
Excessive movement of K+ into cells 
extreme weakness

Question 20

K losses

Answer 20

RENAL 
hyperaldosteronism - adrenal aldosterone secreting tumor 
liquorice 
Diuretics 
Renal tubular acidosis 

GUT 
Vomiting 
diarrhoea 
laxatives 
Ileostmey

Question 21

Treatment - hypokalemia

Answer 21

treat underlying problem
Fro mild hypokalemia - use oral
For severe use IV replacement

Question 22

hyperkalemia

Answer 22

k > 5.0mmol/L 
symptoms 
- fatigue or weakness 
- Parasthesia 
- Nausea and vom 
- Dyspnea 
- Palpitations

Question 23

Pseudohyperkalaemia

Answer 23

in lab tests due to haemolysed sample

Question 24

Causes of hyperkalemia

Answer 24

increased intake

disruption of cell intake

• beta blockers
• acidosis
• rhabdomyolysis

Decreased excretion

• renal failure
• hypoaldosteronism
• ACEi/ARB
• Other drugs

Question 25

Additions disease

Answer 25

opposite of cons tumour
- deficit secretion of adrenal hormones: aldosterone and cortisol
Characteristic hyper pigmented appearance due to excessive ACTH excretion stimulating melanocytes
Symptoms: lethargy, weakness
Weight loss, low BP
hyperkalemia and hyponatremia

Question 26

Hyperkalemia treatment

Answer 26

stabilise action potential 
Push K into cells (by giving intravenous calcium) 
Reduce K absorption 
Increase elimination 
Fix underlying problem

Question 27

Beta agonists

Answer 27

ventolin nebulisers
5mg salbutamol
can do hourly
this also pushes K intracellularly

Question 28

Insulin

Answer 28

pushes K+ intracellularly
10 units, short acting insulin + 5ml dextrose
starts to work in about 10-20 mins peak effect in a few hours

Question 29

How to treat acidosis

Answer 29

oral bicarbonate tablets 840mg 1-3bd/tds
In emergency, IV bicarb 8.4%, 50mL over one hours and repeat

medium term: 
Cation exchange products 
bind to K in gut and increase decal elimination
Calcium resonium 
can be given orally or rectally 

K losing diuretic
Dialysis
- or if rhabdomyalsis