Physiology · Renal, fluids and acid–base

Potassium balance !

Regulation
Exam priority: high

Almost all potassium sits inside cells. Small changes in the blood upset the heart and muscles, so the body controls it closely.

Updated 2026-11-01

Also called: Serum potassium, Kalemia

See it in 3D: Kidneys · Left adrenal gland

What it is

More than 98% of body potassium is inside cells, held there by the Na⁺/K⁺-ATPase. The plasma level (≈ 3.5–5.0 mEq/L) sets the resting potential of nerve and muscle, so it is controlled in two time frames: within minutes, by moving K⁺ into or out of cells; over hours, by adjusting its secretion in the collecting duct.

How it works, step by step

After a meal, absorbed K⁺ moves quickly into cells through the insulin-stimulated Na⁺/K⁺-ATPase.
This prevents a dangerous plasma spike while the kidney has not yet removed it.
Filtered K⁺ is almost all reabsorbed in the proximal tubule (≈ 65%) and thick ascending limb (≈ 25–30%).
The amount excreted is decided in collecting duct principal cells, which secrete K⁺ through ROMK and BK.
High plasma K⁺ directly stimulates aldosterone, which increases ENaC, Na⁺/K⁺-ATPase and K⁺ secretion.
When K⁺ is short, α-intercalated cells reabsorb it with H⁺/K⁺-ATPase and secretion drops to a minimum.

The nephron: segments, transporters and diuretics

Na⁺ reabsorbed ≈ 2–5%Water reabsorbed variable (ADH)

Collecting tubule and duct

What it does: Fine tuning: reabsorbs ≈ 2–5% of Na⁺, secretes K⁺ and H⁺ and reabsorbs water as ADH allows (urine from ≈ 50 to ≈ 1200 mOsm/kg). Principal cells handle Na⁺, K⁺ and water; intercalated cells handle acid–base.
Transporters: Principal: ENaC, ROMK and BK (K⁺ secretion; BK is flow-driven), apical AQP2 (ADH) and basolateral AQP3/4. α-intercalated: H⁺-ATPase and H⁺/K⁺-ATPase (secrete acid). β-intercalated: pendrin (secrete HCO₃⁻). Inner medulla: urea transporters (ADH).
Hormones: Aldosterone (more ENaC, ROMK, Na⁺/K⁺-ATPase and H⁺-ATPase); ADH via the V2 receptor → cAMP → AQP2 insertion; atrial natriuretic peptide curbs Na⁺ reabsorption.
Drugs: ENaC blockers (6) and mineralocorticoid receptor antagonists (7): K⁺-sparing (risk of hyperkalemia). V2 receptor antagonists (8, vaptans): aquaretics.
Disorders: Liddle syndrome (overactive ENaC: hypertension, hypokalemia, low renin and aldosterone); nephrogenic diabetes insipidus (V2 or AQP2, lithium); type 1 distal renal tubular acidosis (H⁺ secretion fails: urine pH > 5.5, hypokalemia, stones) and type 4 (hypoaldosteronism: hyperkalemia); SIADH (excess ADH).

Glomerulus and arterioles
Proximal tubule
Thin descending limb
Thin ascending limb
Thick ascending limb
Distal convoluted tubule
Collecting tubule and duct
Juxtaglomerular apparatus (macula densa)
Cortex
Medulla
Interstitial osmolality (≈ 300 → 1200 mOsm/kg)

Illustrative schematic drawn by Durgical (a long-loop juxtamedullary nephron); proportions and percentages are approximate and not for clinical decisions.

Reference values

Parameter	Value	Note
Plasma K⁺	3.5–5.0 mEq/L
Intracellular K⁺	≈ 140 mEq/L
Total body K⁺	≈ 3500 mEq	> 98% inside cells
Daily renal excretion	≈ 90% of intake	the rest in stool

Approximate values for a healthy adult at rest; each laboratory sets its own ranges.

Regulation

+Insulin: Activates Na⁺/K⁺-ATPase: moves K⁺ into muscle and liver.
+β2 agonists (adrenaline): Move K⁺ into cells.
+Aldosterone: More K⁺ secretion in the collecting duct (and some cell uptake).
+Distal flow and Na⁺ reaching the collecting duct: More K⁺ secretion (loop and thiazide diuretics).
−Acidosis: Moves K⁺ out of cells and reduces its renal secretion.
−Hyperosmolality: Water leaves the cell and drags K⁺ with it (hyperglycemia).

Causes by mechanism

Mechanism	Hyperkalemia	Hypokalemia
Shift between compartments	Insulin lack, acidosis, cell lysis, β blockade	Insulin, β2 agonists, alkalosis
Kidney	Kidney disease, ACE inhibitors/ARBs, K⁺-sparing diuretics, low aldosterone	Loop and thiazide diuretics, aldosterone excess, vomiting
Losses outside the kidney	—	Diarrhea
Spurious	Sample hemolysis	—

Clinical notes

Hyperkalemia partly depolarizes cells, inactivates Na⁺ channels and slows conduction; calcium stabilizes the membrane and insulin with glucose shifts K⁺ in.
In diabetic ketoacidosis, starting insulin drives K⁺ into cells and it can fall dangerously, so it is checked before and during.
Hypokalemia from vomiting is mainly renal loss (aldosterone and alkalosis), not the K⁺ in the vomit.
Hypokalemia increases toxicity of digoxin, which competes for the Na⁺/K⁺-ATPase.

Test yourself

Think of the answer, then tap the question to see it.

Why can a patient with diabetic ketoacidosis have high serum K⁺ with low total body potassium?

Insulin lack and hyperosmolality move K⁺ out of cells while osmotic diuresis loses it in urine. Plasma is high, but the cell store is empty.

Why do loop and thiazide diuretics cause hypokalemia?

They raise the flow and Na⁺ reaching the collecting duct, and hypovolemia activates aldosterone; both increase K⁺ secretion by principal cells.

Why does insulin with glucose lower serum potassium within minutes without changing total potassium?

Insulin activates Na⁺/K⁺-ATPase and moves K⁺ into muscle and liver: it is a shift between compartments, not removal.

What does hyperkalemia do to the resting potential and cardiac conduction?

It makes it less negative; many Na⁺ channels become inactivated, conduction slows (wide QRS) and repolarization speeds up (peaked T waves).

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See it in 3D

The structures of Durgical's 3D anatomy where it happens.

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 26.3 Electrolyte Balance (OpenStax (Rice University), 2022); High potassium level: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Low blood potassium: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 30). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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Representative model, for educational purposes only.