Page created on December 17, 2018. Last updated on May 25, 2023 at 12:27
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:
- Tonicity of the extracellular space
- Physical activity
pH: When acidosis occurs, the body attempts to buffer the increasing plasma H+. One of these is the intracellular buffer, where H+ in the plasma is moved inside cells. To maintain electroneutrality, the cells exchange K+ to the plasma. The total amount og potassium ion in the body doesn’t change, but a larger fraction of it is moved to the plasma, potentially causing hyperkalaemia. Hyperkalaemia reduces the kidney’s ability to excrete ammonia, which may further worsen the acidosis. For every 0.1 unit reduction in blood pH the plasma potassium concentration increases by approximately 0.2 – 2 mM.
The opposite can occur in case of alkalosis. Hydrogen ions are buffered out of the cells, requiring cells to move K+ ions into the cells, potentially causing hypokalaemia.
Reciprocally, an increase in plasma K+ concentration (hyperkalaemia) causes cells to buffer this change by moving K+ ions into the cells. To maintain electroneutrality, the cells exchange H+ to the plasma, potentially causing acidosis. The opposite can occur in case of 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
- 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
- Primary renal tubular disorders (RTA, channelopathies)
- Potassium shift into cells
- 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
- Tubulointerstitial nephritis
- K+ shift out of cells
- 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 hyperkalaemia. 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 to treat severe or acute hyperkalaemia, but can be used for chronic or mild/moderate hyperkalaemia.
12 thoughts on “80. Disorders of potassium balance. Hypo- and hyperkalaemia”
Where does hyperaldosteronism fit in this?
The effect of aldosterone (mineralocorticoids) is explained in the topic. Is there something you feel is missing?
So why you wrote you dont know how??:D
Hyperaldosteronism —> hypokalemia
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
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?
H+ and K+ are not usually excreted together; rather the opposite. The statement is correct; acidosis leads to hyperkalaemia and vice versa.
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+ ?
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.
why does hypokalaemia cause nephrogenic diabetes insipidus?
I googled and it’s apparently not well known exactly how it does.
I have made research on regards to hypokalemia and hyperkalemia in acidosis. Hypokalemia occurs in respiratory acidosis because the kidney filters out H+ in exchange for K+ (that’s what the website says, so I’m guessing both go out together…), and hyperkalemia is caused in metabolic acidosis, since it disrupts the normal exchange of potassium ions between cells and ECM, leading to hyperkalemia itself. Having you said K+ and H+ never go out together of a cell, could you explain further on that? Since other sources say otherwise.
I’ve updated the section under the internal potassium balance to explain the mechanisms better. Is it understandable now, Big Head Daddy?