Potassium

Why intracellular K+ is high

Na/K‑ATPase pumps 3 Na+ out, 2 K+ in → maintains −90 mV resting potential.

How do we regulate high circulating levels of K+? Why?

We shift K+ into the cells until they can be excreted by the kidneys or GI system. High levels of K+ can lead to arrythmias

Effect of insulin on K+

Activates PI3K → aPKC → inserts Na/K‑ATPase + activates Akt which inserts GLUT4→ shifts K+ INTO cells.

Effect of β2‑agonists on K+

↑ cAMP/PKA → ↑ Na/K‑ATPase → shifts K+ INTO cells.

Effect of α‑agonists on K+

Decreases Na/K‑ATPase → K+ OUT of cells.

Effect of mineral (inorganic) acidosis on K+

↓ extracellular pH → ↓ Na/H exchanger1/Na/HCO3 exchanger → ↓ intracellular Na → ↓ Na/K‑ATPase → K+ OUT of cells.

Effect of organic acidosis on K+

OA− enters cell via MCT → ↑ intracellular Na → maintains Na/K‑ATPase → NO significant change in serum K+.

Effect of hyperosmolarity on K+

Water leaves cells → solvent drag pulls K+ OUT → hyperkalemia.

Effect of exercise on K+

K+ released from contracting muscle → transient ↑ serum K+.

Effect of cell lysis on K+

Massive K+ release → hyperkalemia (TLS, rhabdo, hemolysis).

Effect of digitalis on K+

Inhibits Na/K‑ATPase → K+ OUT → hyperkalemia.

Renal K+ handling (overview)

PT reabsorbs 65–70%, TAL reabsorbs 20%, DT/CCD secrete K+, α‑intercalated reabsorb K+ in hypokalemia.

PT K+ reabsorption mechanism

Passive paracellular via solvent drag + lumen‑positive voltage.

TAL K+ handling

NKCC2 reabsorbs K+, ROMK recycles K+ to lumen → creates lumen‑positive voltage → paracellular K+ reabsorption.

Effect of loop diuretics on K+

Inhibit NKCC2 → collapse lumen‑positive gradient → ↓ K+ reabsorption → hypokalemia.

Early DCT K+ handling

NaCl cotransporter (NCC) → ↑ intracellular Cl− → activates K‑Cl cotransporter → K+ secretion.

Effect of thiazides on K+

Inhibit NCC → ↑ Na delivery to CCD → ↑ K+ secretion → hypokalemia.

Collecting Duct principal cell K+ secretion

ENaC reabsorbs Na+ → lumen becomes negative → ROMK/Maxi‑K secrete K+.

α‑intercalated cell K+ handling

H‑K ATPase reabsorbs K+ (↑ in hypokalemia, ↓ in hyperkalemia).

Major regulators of renal K+ secretion

Distal Na delivery, tubular flow rate, aldosterone, extracellular K+.

Effect of distal Na delivery

↑ Na → ↑ ENaC activity → ↑ lumen negativity → ↑ K+ secretion.

Effect of tubular flow rate on K+

High flow washes K+ away → ↑ gradient → ↑ K+ secretion.

Effect of aldosterone

↑ ENaC, ↑ Na/K‑ATPase, ↑ ROMK → ↑ K+ secretion.

Effect of extracellular K+

Directly stimulates aldosterone + ↑ Na/K‑ATPase → ↑ K+ secretion.

Causes of hypokalemia (overview)

Poor intake, shifts into cells, renal losses, GI losses, skin losses, pseudohypokalemia.

Hypokalemia: intracellular shifts

Insulin, β‑agonists, alkalosis.

Hypokalemia: renal losses

Thiazides, loops, amphotericin B, cisplatin, hyperaldosteronism, Bartter, Gitelman, Liddle, RTA I/II.

Hypokalemia: GI losses

Diarrhea, vomiting, NG suction, laxatives.

Hypokalemia: pseudohypokalemia

Extreme leukocytosis (AML).

Hypokalemia clinical manifestations

Weakness, cramps, rhabdo, ileus, respiratory failure, arrhythmias.

Hypokalemia EKG findings

Flattened T waves, ST depression, prominent U waves, prolonged QU interval.

Hypokalemia treatment (general)

Correct Mg first, stop diuretics, give KCl, treat underlying cause.

Causes of hyperkalemia (overview)

Excess intake, shifts out of cells, decreased excretion, pseudohyperkalemia.

Hyperkalemia: intracellular shifts

Acidosis (mineral), insulin deficiency, β‑blockers, digoxin toxicity, hyperosmolarity, exercise, cell lysis.

Hyperkalemia: decreased excretion

CKD, AKI, hypoaldosteronism, ACEi, ARBs, NSAIDs, K‑sparing diuretics, TMP‑SMX, cyclosporine, tacrolimus.

Hyperkalemia: pseudohyperkalemia

Hemolysis(bc lysed cell releases K), thrombocytosis, leukocytosis (CLL).

Hyperkalemia clinical manifestations

Muscle weakness, paralysis, arrhythmias, cardiac arrest.

Hyperkalemia EKG findings

Peaked T waves → prolonged PR → loss of P → wide QRS → sine wave → asystole.

Hyperkalemia emergency stabilization

IV calcium gluconate or CaCl2 → stabilizes cardiac membrane.

Hyperkalemia redistribution therapies (what do you do if you C A BIG K)

IV insulin + dextrose, β2‑agonists, sodium bicarbonate (if acidotic).=>shift K into cell (CABIGK= Calcium gluconate, Albuterol(b2 agonist), Bicarb, Insulin, Glucose, Kayexalate(K+ binder))

Hyperkalemia elimination therapies

Loop diuretics, K‑binders (SPS, patiromer, SZC), dialysis.

Drugs causing hyperkalemia

ACEi, ARBs, spironolactone, eplerenone, amiloride, triamterene, TMP‑SMX, NSAIDs, heparin, cyclosporine, tacrolimus, β‑blockers, digoxin.

Why Mg deficiency worsens hypokalemia

Mg inhibits ROMK→allows for excess K+ to leak out into the urine→cant replenish and maintain internal K+

Why diarrhea causes low urinary K+

GI loss → low serum K+ → low filtered load → low urinary K+.

Expected K+ changes in acid‑base disorders

Mineral acidosis → ↑ K+

Expected K+ changes with insulin therapy

Insulin shifts K+ INTO cells → ↓ serum K+.

Expected K+ changes with β‑blockers

Block β2 → ↓ Na/K‑ATPase → ↑ serum K+.

Expected K+ changes with digoxin

Inhibits Na/K‑ATPase → ↑ serum K+.

Expected K+ changes with aldosterone

↑ K+ secretion → ↓ serum K+.

Expected K+ changes with hypoaldosteronism

↓ K+ secretion → ↑ serum K+.