Control of Potassium

Question 1

What is the distribution of potassium in body fluids?

Answer 1

Total 3500mmol.
Mainly in the skeletal muscle cells, liver, RBC and bone.
98% in ICF (120-150mmol/L).
2% in ECF (3.5-5mmol/L).

Question 2

How is the difference between ICF and ECF of [K+] maintained?

Answer 2

By Na-K-ATPase.

Question 3

Why is maintaining ECF [K+] critical?

Answer 3

1. K+ has a serious impact on resting membrane potentials.
2. Subsequently K+ has an effect on the excitability of cardiac tissue.
3. This means there is a risk of life threatening arrhythmias with hyperkalaemia and hypokalaemia.

Question 4

What is the effect of [K+] on the resting membrane potential?

Answer 4

There is a concentration gradient for K+ to move out of the cell.
There is an electrical gradient driving K+ back into the cell.
This creates a resting membrane potential of around -90mV.

Question 5

What happens to the resting membrane potential in different concentrations of K+?

Answer 5

Hypokalaemia: causes a decrease in RMP (more negative).
Hyperkalaemia: causes an increase in RMP (more positive).

Question 6

How is ECF [K+] regulated?

Answer 6

1. Immediately by the internal balance between ICF and ECF.

2. In the long term by overall K+ balance which is external and involves adjusting renal K+ excretion.

Question 7

Describe the events of K+ following a meal.

Answer 7

The intestine and colon absorb dietary K+.
4/5ths of the K+ which has now been absorbed into the ECF will move into cells within minutes.
After a slight delay the kidneys begin to excrete K+. Excretion is complete in 6-12 hours.
Signals from the gut influence meal driven potassium excretion also.

Question 8

How long does it take the kidney to excrete K?

Answer 8

6-12hours.

Question 9

How is [K+] internally balanced?

Answer 9

1. Movement of K+ from the ECF into cells via Na-K-ATPase.

2. Movement of K+ out of cells into the ECF via K+ channels (determine the K+ permeability of the cell membrane).

Question 10

What factors increase K+ uptake into cells?

Answer 10

1. Hormones via Na-K-ATPase: insulin, aldosterone and catecholamines.
2. Increased [K+] in ECF, which creates a concentration gradient.
3. Alkalosis: a low ECF [H+] causes H+ to leave the cell and thus K+ to enter the cells.

Question 11

What factors promote K+ shift out of cells?

Answer 11

1. Exercise.
2. Cell lysis.
3. Increase in ECF Osmolality, can cause water to come out of cells and K to follow.
4. Decreased [K+] ECF.
5. Acidosis: Increases in [H+] in the ECF causes H+ to move into cells and K+ to move out of cells.

Question 12

How does insulin increase K+ cellular uptake?

Answer 12

K+ in the splanchnic blood stimulate insulin secretion by the pancreas.
Insulin increases Na-K-ATPase activity which increases K+ uptake into muscle cells and the liver.

Question 13

What is the clinical use of insulin in terms of K+?

Answer 13

Insulin and dextrose can be used to treat hyperkalaemia.

Question 14

How does aldosterone increase K+ cellular uptake?

Answer 14

K+ in blood stimulates aldosterone secretion.

This stimulates the uptake of K+ via Na-K-ATPase.

Question 15

How does Catecholamines increase K+ cellular uptake?

Answer 15

Act via B2 adrenoreceptors.

This stimulates Na-K-ATPase and cellular uptake of K+.

Question 16

How does exercise increase K+ back into the ECF?

Answer 16

Net release of K+ during the recovery phase of action potential, K+ exits the cell.
There is also skeletal muscle damage during exercise releasing K+.
There is subsequent uptake b y non-contracting tissues to prevent dangerously high hyperkalaemia.
Exercise also increases catecholamines which offset ECF [K+] rise (increase K+ uptake by other cells).
Cessation of exercise results in a rapid plasma decrease in potassium.

Question 17

What 2 factors stop exercise from causing severe hyperkalaemia?

Answer 17

1. Catecholamine release.

2. Non-contracting tissues uptake some K+.

Question 18

Why can acidosis cause hyperkalaemia?

Answer 18

H+ shift into cells (due to conc gradient). This causes K+ to leave the cell into ECF and thus cause hyperkalaemia.

Question 19

Why can alkalosis cause hypokalaemia?

Answer 19

H+ shift out of cells (due to conc gradient). This causes K+ to enter cells and thus less K+ is in the ECF so there is hypokalaemia.

Question 20

Why can hyperkalaemia cause acidosis?

Answer 20

K+ high in the ECF means it enters the cell. This causes H+ to leave cells and thus acidosis.

Question 21

Why can hypokalaemia cause alkalosis?

Answer 21

K+ is low so K+ leaves the cells. This causes H+ to enter cells and thus there is low ECF H+ and so alkalosis.

Question 22

Explain how external balance controls [K+]?

Answer 22

This process is slower. It takes 6-12 hours to excrete a load of K+. It does it by controlling total body potassium content over the longer term. It regulates K+ secretion in the late DT and cortical collecting duct principal cells/
It is all done via the Na-K-ATPase on the basolateral membrane. This transporter increases the intracellular K+ and decreases the intracellular Na+.
High intracellular K+ creates a chemical gradient for secretion.
Na+ moves into the lumen into the cell down its concentration gradient (via apical ENaC) which creates an electrical gradient.
Both these gradients allow a favourable movement of K+ secretion via apical K+ channels.

Question 23

What are the factors that affect K+ secretion by principal cells?

Answer 23

Tubular Factors:
1. ECF [K+]: directly stimulates Na-K-ATPase, increasing the permeability of apical K+ channels and stimulating aldosterone secretion.
2. Aldosterone stimulated by high ECF [K+]. Increases transcription of relevant proteins (Na-K-ATPase, K and ENac)
3. Acid Base Status: Acidosis decreases K+ secretion (H+ move into cells and K+ move out of cells into ECF) by inhibiting Na-K-ATPase and alkalosis does the opposite.
Luminal Factors:
4. Increases distal tubular flow rate washes away the luminal K+ and so increases K+ loss.
5. Increased Na delivery to the distal tubule means more Na absorbed and so more K+ lost.

Question 24

Describe the K+ absorption by intercalated cells the distal tubule and cortical collecting duct.

Answer 24

K+ absorbed by the intercalated cells by an active process mediated by H+-K+-ATPase in the apical membrane of the lumen.

Question 25

What do changes in ECF [K+] cause?

Answer 25

1. Anterior the cell membrane resting potential.
2. Alter neuromuscular excitability: causing problems with cardiac conduction, pacemaker automaticity, neuronal function, skeletal muscle and smooth muscle function.
3. This consequently causes arrhythmias, cardiac arrest and muscle paralysis.

Question 26

What are the causes of hyperakalamia?

Answer 26

1. Increased intake if renal dysfunction present/IV dose incorrect.
2. Decreased renal excretion: Injury, drugs.
   Internal shifts:
3. Diabetic ketoacidosis: no insulin so no K+ absorption into cells, as well as hyperosmolariy and metabolic acidosis.
4. Cell lysis.
5. Metabolic acidosis.
6. Exercise.

Question 27

What are the Clinical Features of Hyperkalaemia?

Answer 27

1. Heart: altered excitability can cause arrhythmias and heart block. This is because it depolarises the cardiac tissue so the more fact Na channels remain in the inactive form so the heart is less excitable. ECG: high T wave (gets progressively worst), eventual VF.
2. Gastrointestinal neuromuscular dysfunction: paralytic ileus.
3. Acidosis.

Question 28

What is the emergency treatment of hyperkalaemia?

Answer 28

1. Reduce the K+ effect on the heart using IV calcium gluconate.
2. Shift K+ into the ICF using glucose and insulin. Or by using a nebulised beta agonist like salbutamol.
3. Remove the excess K+ by dialysis.

Question 29

What is the long term treatment of hyperkalaemia?

Answer 29

1. Treat the cause, e.g. stop medications.
2. Reduce the intake.
3. Measures to remove excess K+ by dialysis or oral K+ binding resins in the gut.

Question 30

How do you define hyperkalaemia?

Answer 30

A [K+] in the ECF of more than 5.0mmol/L.

Question 31

How do you define hypokalaemia?

Answer 31

A [K+] in the ECF of less. than 3.5mmol/L.

Question 32

What are the causes of hypokalaemia?

Answer 32

1. Problems of external balance such as excessive loss via the GI (diarrhoea, vomiting) or the kidneys (due to high aldosterone, diuretics or diabetes (osmotic diuresis)).
2. Problems of the internal balance where the potassium shifts into the ICF like in metabolic alkalosis.

Question 33

What are the clinical features of Hypokalaemia?

Answer 33

1. Heart: altered excitability which can cause arrhythmias as the RMP is hyperpolarised so there is more fact Na channels available in the active form making the heart more excitable. On an ECG this will show as a decreased T wave and a high U wave. Increase in severity with lower K+.
2. Gastrointestinal neuromuscular dysfunction causing a paralytic ileus.
3. Skeletal muscle: neuromuscular dysfunction creating muscle weakness.
4. Renal: unresponsive to ADH-> nephorgenic.

Question 34

How do you treat hypokalaemia?

Answer 34

1. Treat the cause.
2. Potassium replacement- IV oral.
3. If due to increased mineralocorticoid activity: block system with potassium spearing diuretics.