Potassium handling

What it normally does

• About 98% of the body's potassium sits inside cells. That steep gradient across the membrane is what holds nerve and muscle at their negative resting voltage (resting membrane potential).

  A small change in blood potassium changes how easily heart muscle fires — which is where the ECG changes of hyperkalaemia come from.

• The kidney filters potassium freely and takes nearly all of it back in the proximal tubule and loop of Henle. The amount that actually leaves the body is decided further downstream, in the late distal tubule, connecting tubule and cortical collecting duct, where aldosterone makes the principal cell pull sodium in through a channel (ENaC), leaving the lumen electrically negative, and that negative lumen drags potassium out through its own channel (ROMK). High tubular flow adds a second, flow-activated potassium channel (BK).

  Potassium excretion tracks aldosterone and tracks how much sodium and fluid reach that segment — so anything touching either one moves potassium.

• Insulin and adrenaline (through the beta-2 receptor) push potassium into cells by driving the sodium-potassium pump (Na+/K+-ATPase) in muscle. Neither removes any potassium from the body.

  It explains the emergency treatment for hyperkalaemia, and explains why a measured potassium can lie badly about total body stores.

• Hydrogen and potassium trade places across the cell membrane. When the blood turns acidic with a mineral acid (as in a hyperchloraemic acidosis), hydrogen moves into cells and potassium comes out; alkalosis does the reverse. Organic acidoses such as lactic acidosis and ketoacidosis shift potassium far less, because the anion crosses the membrane with the acid — in ketoacidosis the hyperkalaemia owes more to insulin deficiency and hyperosmolality than to the pH itself. Aldosterone drives hydrogen secretion by the intercalated cells of the same segment in which the principal cells secrete potassium.

  A hyperchloraemic acidosis inflates the measured potassium and alkalosis deflates it, and aldosterone disorders characteristically carry a matching acid-base picture — although it may be mild or absent when the disorder is mild.

What goes wrong

• Hyperkalaemia and its ECG← from “About 98% of the body's potassium sits inside …”

  Potassium cannot get out. Usually the kidney has failed (acute kidney injury or chronic kidney disease), so the filtered load and the sodium and fluid delivery that drive distal secretion both fall — but the remaining nephrons up-regulate secretion, which is why chronic kidney disease alone rarely causes hyperkalaemia until eGFR is very low or urine output drops; at a moderately reduced eGFR, look for the added drug, the potassium load or the acidosis. Extracellular potassium rises, the gradient across the membrane shrinks and the resting voltage drifts up towards threshold. Sodium channels recover from inactivation only at negative voltages, so they sit inactivated and conduction slows and widens. At the same time the higher potassium conductance makes repolarisation abrupt.

  Potassium above about 6.5 mmol/L, or any ECG change at all, is an emergency; the usual causes are kidney failure and the ACE inhibitor plus spironolactone plus NSAID combination, with potassium supplements, trimethoprim and tissue breakdown (rhabdomyolysis, tumour lysis, haemolysis) close behind. Before treating a well patient with a flawless ECG, ask whether the sample was haemolysed, clenched-fist drawn or delayed to the lab (pseudohyperkalaemia). End-stage kidney disease is several times more common in Aboriginal and Torres Strait Islander Australians, and much higher again in remote communities, so this is a presentation you will meet.

  You would find: The ECG changes broadly in this order: tall narrow peaked T waves, then a long PR with flattened or absent P waves, then a broad QRS, then the QRS merging with the T into a sine wave, then arrest. The order is a teaching sequence, not a promise — a patient can arrive at a broad complex rhythm with no warning peaked T waves at all, so a normal-looking ECG does not exclude hyperkalaemia. Weakness and paraesthesiae are late and unreliable.

• Too little aldosterone effect (Addison disease, type 4 renal tubular acidosis)← from “The kidney filters potassium freely and takes …”

  Without aldosterone the principal cell has fewer active sodium channels, so the lumen never goes properly negative and neither potassium nor hydrogen is efficiently secreted. In Addison disease the adrenal cortex is destroyed, autoimmune in most Australian cases. In diabetic kidney disease the same picture comes from low renin and therefore low aldosterone (hyporeninaemic hypoaldosteronism, type 4 RTA); drugs that block the axis reproduce it closely.

  Hyperkalaemia plus hyponatraemia plus postural hypotension is Addison until proven otherwise — a short synacthen test settles it, and in a suspected crisis treatment comes before confirmation. Aldosterone deficiency brings acidosis with it because hydrogen and potassium excretion depend on the same electrical gradient in the same segment.

  You would find: Addison: high potassium with a low sodium, postural drop in blood pressure, fatigue, weight loss and pigmented skin creases and buccal mucosa. Type 4 RTA: a stubborn mild hyperkalaemia with a normal anion gap acidosis in a diabetic whose creatinine is only modestly raised.

• Too much aldosterone effect — hypokalaemia with alkalosis← from “The kidney filters potassium freely and takes …”

  A strongly negative lumen drives both potassium and hydrogen into the urine. Primary hyperaldosteronism (Conn syndrome) does it directly. Loop and thiazide diuretics do it indirectly by dumping extra sodium and flow onto the collecting duct, with volume depletion raising aldosterone on top. Vomiting does it twice over: volume loss raises aldosterone, and the lost gastric acid starts the alkalosis that shifts potassium into cells.

  Primary hyperaldosteronism is a common and treatable cause of resistant hypertension, not a rarity — and most patients with it are normokalaemic, so a normal potassium does not exclude it. Interfering drugs (spironolactone above all, and beta-blockers and ACE inhibitors or ARBs to a lesser degree) distort the aldosterone-to-renin ratio, so check how to prepare the patient before ordering it. Magnesium matters too — intracellular magnesium normally plugs ROMK, so a low magnesium unplugs it, wastes potassium and makes the hypokalaemia refractory to potassium alone.

  You would find: Muscle weakness, cramps, constipation and polyuria. ECG shows flattened T waves, prominent U waves and a long apparent QT. Hypertension with an unexplained low potassium means screening for Conn with an aldosterone-to-renin ratio.

• The diabetic ketoacidosis potassium trap← from “Hydrogen and potassium trade places across the…”

  Insulin deficiency and hyperosmolality drive potassium out of cells, and the osmotic diuresis then flushes it out in the urine for hours or days. Total body potassium is heavily depleted while the plasma level, propped up by the shift, reads normal or high. Give insulin and fluid and the shift reverses within minutes to hours.

  Potassium is checked before the first dose of insulin. Below about 3.5 mmol/L, guidelines have potassium replaced before insulin is started — insulin into a hypokalaemic patient risks arrhythmia. The actual replacement follows the local DKA protocol.

  You would find: A patient in DKA with a reassuring potassium of 4.0 mmol/L is severely depleted. After insulin starts, the potassium falls fast and needs hourly attention.

What we give, and how it works

Open a drug to see what it binds, what that does to the cell, and what you then see in the patient.