80. Disorders of potassium balance. Hypo- and hyperkalaemia

Page created on December 17, 2018. Last updated on April 28, 2021 at 09:41

Potassium in the body

98% of all potassium in the body is intracellular. In the intracellular space is the concentration 140 – 160 mM, while in the extracellular space it is just 3.5 – 5.5 mM.

The serum potassium level depends in two things:

  • The internal potassium balance, the balance between the intracellular and extracellular compartments
  • The external potassium balance, the balance between potassium intake and potassium loss
The internal potassium balance

The internal balance depends on 6 things:

  • pH
  • Tonicity of the extracellular space
  • Insulin
  • Catecholamines
  • Mineralocorticoids
  • Physical activity

pH: Cells have the possibility to excrete K+ in exchange for H+ and visa versa. If the extracellular H+ concentration is low (alkalosis) will H+ be pumped out of cells while K+ will be pumped into cells. If the extracellular H+ level is high (acidosis) will H+ be pumped into cells while K+ will be pumped out. Acidosis can therefore cause hyperkalaemia while alkalosis can cause hypokalaemia.

Tonicity: When the extracellular space is hypertonic (due to increased sodium or glucose concentration for example) will water flow out of cells and into the EC space. Because the K+ level inside the cell doesn’t change will the K+ concentration increase, as the cells have lost water. This concentration increase causes K+ to flow out of the cell, potentially causing hyperkalaemia.

Insulin enhances Na+/K+ ATPase activity, causing K+ to enter the cells. In fact, when there is a hyperkalaemia that should be quickly normalized it is common to give insulin and glucose simultaneously. This doesn’t really fix the elevated K+ level in the body though, it just “hides” the potassium inside cells.

Catecholamines also enhances Na+/K+ ATPase activity, via β2-receptors. α-receptors decrease the activity.

Mineralocorticoids contribute to the balance. I don’t know how it contributes to the internal balance (book doesn’t explain). Their effect on the external balance is much more important.

Physical activity causes K+ outflow from muscle cells.

The external potassium balance

The daily intake of food is ca 40 – 120 mmol K+. This extra potassium reaches the extracellular space and not the cells in normal cases. 90% of the lost potassium is excreted by the kidneys, the remaining through the GI tract.

The external balance depends on 5 things:

  • K+ intake
  • Mineralocorticoids
  • Filtration
  • pH
  • GI excretion

K+ intake is counter-regulated by kidney and GI excretion, so even a high potassium intake isn’t dangerous (unless it’s intravenous). In end-stage renal failure, when the GFR < 5 mL/min even a few bananas can cause severe hyperkalaemia.

Mineralocorticoids play a much larger role in the external balance than the internal. Aldosterone and some of its weaker precursors enhance Na+/K+ and Na+/H+ exchange in the distal tubules and collecting duct. This causes K+ and H+ loss.

The GFR determines how much K+ is filtered. When it’s increased will more water and sodium reach the distal tubules, which increases Na+/K+ exchange, causing sodium to be reabsorbed and more potassium to be excreted. Increased flow rate, such as in osmotic diuresis, inhibits K+ reabsorption. Increased level of anions in the filtrate, like bicarbonate, increases K+ excretion because of electroneutrality.

pH also influences the potassium excretion. Renal K+ excretion decreases in acidosis and increases in alkalosis.

GI excretion only accounts for 10% of potassium loss in healthy people, but in severe renal failure may this number go up to 50% to compensate for the failing kidneys.


Hypokalaemia is mild when between 3,5 – 3,0 mM, moderate between 2,9 – 2,5 mM, and severe below 2,5 mM.

Most important causes:

  • Increased loss of potassium
    • Diuretics (loop diuretics, thiazide diuretics) – most common cause
    • Diarrhoea, vomiting
    • Hyperaldosteronism
    • Hypercortisolism
    • Primary renal tubular disorders (RTA, channelopathies)
  • Potassium shift into cells
    • Alkalosis
    • Exogenous insulin
  • Decreased potassium intake

Consequences of hypokalaemia:

  • Development of metabolic alkalosis
  • Hyperpolarized membranes (membrane potential becomes more negative)
    • Muscle weakness
    • Muscle cramps, pain
    • Cardiac arrhythmias
  • ECG changes
    • Shallow or inverted T-wave
    • Prominent U-wave
    • ST depression
  • Polyuria (hypokalaemia causes nephrogenic diabetes insipidus where the kidney responds less to ADH)


It is treated by treating the underlying cause, as well as supplying potassium orally by diet or supplement, or IV if necessary.


Hyperkalaemia is mild when between 5,0 – 6,0 mM, moderate between 6,1 – 6,9 mM, and severe above 7,0 mM.


  • Pseudohyperkalaemia (haemolysis during blood draw)
  • Decreased loss
    • Renal insufficiency (CKD or AKI)
    • Addison disease
    • Potassium-sparing diuretics
    • RAAS inhibitors
    • NSAIDs
    • Tubulointerstitial nephritis
  • K+ shift out of cells
    • Acidosis
    • Beta blocker
    • Cell lysis (tumour lysis syndrome, rhabdomyolysis, haemolysis)
    • Increased intake (only in case of renal disease)


  • Development of metabolic acidosis
  • Hypopolarized membranes (membrane potential becomes less negative)
    • Muscle weakness
    • Muscle cramps, pain
    • Cardiac arrhythmias
  • ECG changes
    • Peaked T-wave
    • ST elevation
    • Wide QRS


Calcium gluconate infusion is used to stabilize the membrane potential, which prevents development of cardiac arrhythmias, but does not treat the underlying hypokalaemia. Giving an infusion of insulin + glucose causes an intracellular shift of potassium and can be used in acute cases, as can giving loop diuretics with a fluid infusion. In very severe cases, dialysis is required.

Oral potassium binders are drugs given orally which bind potassium in the GI tract and prevent it from being absorbed or reabsorbed. It has a slow onset of effect and can therefore not be used (alone) to treat hyperkalaemia.

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79. Respiratory acidosis and alkalosis. Causes, compensation, consequences

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81. States of decreased extracellular volume, and their consequences

Parent page:
Pathophysiology 1

10 thoughts on “80. Disorders of potassium balance. Hypo- and hyperkalaemia”

    1. The effect of aldosterone (mineralocorticoids) is explained in the topic. Is there something you feel is missing?

      1. Hi dear
        So why you wrote you dont know how??:D
        Hyperaldosteronism —> hypokalemia
        Hypoaldosteronism—-> hyperkalemia

  1. Aha got it now bc that reason is for external potassium balance , as internal balance is between cell and blood.. sorry then my bad:D

  2. Hi!

    Maybe i’m wrong, but in the external potassium balance, you write that pH is affecting K+ balance in this way: decreased excretion during acidosis, and increased in alkalosis. But let’s say in acidosis we want to get rid of H+, and therefore also K+ is excreted (as they are usually excreted together), wouldn’t the opposite make more sense?

    1. H+ and K+ are not usually excreted together; rather the opposite. The statement is correct; acidosis leads to hyperkalaemia and vice versa.

  3. Hii,
    Happy new year
    I’m just confused, why renal K+ excretion decrease in acidosis while acidosis causes hyperkalaemia ? Don’t we want to get ride of the K+ ?

    1. Happy new year!

      The mechanism of this is very complicated, but one way to think about it is this: K+ and H+ can never be moved out or in of a cell together – they have to move in opposite directions. So in acidosis, where the first priority is to excrete more H+, the kidney does this at the expense of K+ excretion. The mechanism of this is complicated, but if you’re interested you can read more about it here and here.

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