Potassium CLINICAL CHEMISTRYDr.

AHMED JALAL

POTASSIUM HOMEOSTASIS
The total amount of potassium in the body is about 3000 mmol, of which about 98 per
cent is intracellular. For this reason the plasma potassium concentration is a poor
indicator of the total body content.

Factors affecting plasma potassium concentration

The intracellular potassium ion concentration ([K+])is large and provides a reservoir
for the extracellular compartment. Consequently changes in water balance have little
direct effect on the plasma [K+], unlike plasma [Na+]. The normal potassium intake is
about 60–100 mmol/ day. Potassium enters and leaves the extracellular compartment
by three main routes:

- the intestine,

- the kidneys,

- the membranes of all other cells.

The intestine

Potassium is principally absorbed in the small intestine. Dietary intake replaces net
urinary and faecal loss. Prolonged starvation can cause or aggravate potassium
depletion leading to hypokalaemia. Excessive intestinal potassium loss can occur in
diarrhoea, ileostomy fluid or through fistulae.

The kidneys

Potassium is filtered by the glomeruli and, owing to the huge volume of the filtrate,
Potassium is normally almost completely reabsorbed in the proximal tubules. Damage
to these may cause potassium depletion. Potassium is secreted in the distal tubules and
collecting ducts in exchange for Na+; hydrogen ions (H+) compete with potassium
ions (K+). Aldosterone stimulates both exchange mechanisms. If the proximal tubules
are functioning normally, potassium loss in the urine depends on three factors:

1. The amount of sodium available for exchange: this depends on the glomerular
filtration rate, filtered sodium load, and sodium reabsorption from the proximal
tubules and loops of Henle.

2. The circulating aldosterone concentration: this is increased following fluid loss,

with volume contraction, which usually accompanies intestinal loss of potassium, and
in most conditions for which patients are receiving diuretic therapy.

3. The relative amounts of H+ and K+ in the cells of the distal tubules and collecting
ducts, and the ability to secrete H+ in exchange for Na+: this may be impaired during
treatment with carbonate dehydratase (CD) inhibitors .
 Potassium CLINICAL CHEMISTRYDr. AHMED JALAL

The cell membranes

The Na+/K+ adenosine triphosphatase (ATPase) ‘pump’ on cell surfaces maintains a

high intracellular [K+]. This exchanges three Na+ ions from cells in exchange for two
K+ ions in the extracellular fluid (ECF), thus establishing an electrochemical gradient
across the cell membrane, with a net positive charge in the ECF. The loss of K+ from
cells down the concentration gradient is opposed by this electrochemical gradient.
Potassium is also exchanged for H+.

A small shift of K+ out of cells may cause a significant rise in plasma concentrations,
whether in vivo or in vitro. In the latter situation, the artefactual hyperkalaemia due to
haemolysed or old specimens may be misinterpreted and should be avoided. Usually
the shift of K+ across cell membranes is accompanied by a shift of Na+ in the
opposite direction, but the percentage change in extracellular [Na+] is much less than
that of K+. Increased uptake and net gain of K+ by cells may occur in alkalosis due to
increased uptake by cells and increased urinary loss. Insulin enhances the cellular
uptake of glucose and potassium. Hyperkalaemia stimulates insulin secretion and
hypokalaemia inhibits it. This effect may be used to treat hyperkalaemia by giving
exogenous insulin/glucose infusion.

Catecholamines have a similar action, and it has been suggested that this may
contribute to the hypokalaemia sometimes found after the stress of myocardial
infarction. β-adrenergic stimulation increases cellular potassium uptake by stimulating
the Na+/K+-ATPase ‘pump’. β-blockade increases plasma potassium concentration
and b-agonists decrease it, an effect that is independent of body potassium stores.
Synthesis of Na+/K+-ATPase is stimulated by thyroxine, which may contribute to the
hypokalaemia sometimes associated with hyperthyroidism.

Relationship between hydrogen and potassium ions

The extracellular [H+] affects the entry of potassium into all cells. Changes in the
relative proportions of K+ and H+ in distal renal tubular cells affect the urinary loss of
potassium. There is a reciprocal relationship between K+ and H+:
 Potassium CLINICAL CHEMISTRYDr. AHMED JALAL

- In acidosis, increased loss of potassium from cells into the ECF coupled with
reduced urinary secretion of potassium causes hyperkalaemia.

- In alkalosis, net increased uptake of potassium into cells and increased urinary
potassium loss cause hypokalaemia.

In the kidney, Na+ derived from the luminal fl uid is pumped through the cell in
exchange for either K+ or H+. If K+ is lost from the ECF, it passes down the
increased concentration gradient, so reducing its intracellular content. Unless there is
renal tubular cell damage, Na+ are reabsorbed in exchange for fewer K+ and more H+
than usual. For each H+ formed within the tubular cell by the CD mechanism, one
bicarbonate ion is produced.
As more H+ is secreted into the urine, the reaction is increased and more HCO3 – is
generated, passing into the ECF accompanied by the reabsorbed Na+. The result is an
extracellular alkalosis and acid urine. Therefore, chronic potassium depletion is
usually accompanied by a high plasma bicarbonate concentration. The combination of
hypokalaemia and a high plasma bicarbonate concentration is more likely to be due to
K+ depletion than to metabolic alkalosis.
Potassium and diuretic therapy
Diuretics may be used to treat hypertension as well as oedema, for example in cardiac
failure. They can be divided into two principal groups, based upon their site of action.
 Potassium CLINICAL CHEMISTRYDr. AHMED JALAL

- Potassium-losing diuretics increase the sodium load on the distal tubules and
collecting ducts with enhanced Na+/K+ exchange. This may result in hypokalaemia.
– Loop diuretics, such as furosemide or bumetanide, inhibit sodium reabsorption from
the ascending limb of the loops of Henle.
– Thiazides act at the junction of the loops and the distal tubules, which are
sometimes called the ‘cortical diluting segments’.
– Carbonate dehydratase inhibitors, such as acetazolamide, are rarely used as diuretics
but are still used to treat glaucoma. They may cause a hypokalaemic hyperchloraemic
acidosis.
- Potassium-sparing diuretics.
– Diuretics that inhibit either aldosterone directly or the exchange mechanisms in the
distal tubules and collecting ducts cause potassium retention and may lead to
hyperkalaemia, especially if glomerular function is impaired.
Potassium-sparing/-retaining diuretics include spironolactone, a competitive
aldosterone antagonist.
– Other potassium-sparing diuretics include amiloride and triamterene, which are
direct inhibitors of the Na+/K+ exchange mechanism in the distal tubules.
Potassium-sparing diuretics can be used together with those causing potassium loss
when hypokalaemia cannot be controlled by potassium supplementation. Used alone,
they have only a weak diuretic action. Beware of giving potassium supplements to
patients taking potassium-sparing diuretics or angiotensin-converting enzyme (ACE)
inhibitors or angiotensin II receptor blockers (ARBs) because of the risk of
hyperkalaemia.