II-19. Potassium (K+) balance disorders

カリウム（K+）平衡の異常

K⁺ Homeostasis

Intracellular: 98% of body K⁺ (~150 mmol/L) — critical for protein synthesis
Extracellular: 2% (3.5–5 mmol/L) — tightly controlled, needed for excitable cells
Falling/rising K⁺ hyperpolarizes/depolarizes membranes → affects excitability → cardiac arrhythmias
Regulation: renal excretion + transcellular shift. Insulin drives K⁺ into cells (Na⁺/K⁺ ATPase), with circadian peak excretion at noon

Renal control

Aldosterone-dependent (collecting duct): ↑ENaC + Na⁺/K⁺ ATPase → Na⁺ reabsorption + K⁺ excretion via ROMK
Aldosterone-independent: hyperkalemia ↓NCC, ↑tubular flow, K⁺ depletion → H⁺/K⁺ ATPase → H⁺ excretion + K⁺ reabsorption (→ hypokalemic alkalosis)

Hyperkalemia ([K⁺] > 5.5 mmol/L)

Causes

Excessive intake (rarely alone): exogenous (K⁺-rich food, supplements, transfusion, penicillin G) or endogenous (exercise, hemolysis, GI bleed, rhabdomyolysis)
Impaired renal excretion (most common — acute & chronic renal failure): tubular damage/fibrosis, hyporeninemic hypoaldosteronism (diabetic nephropathy, lupus nephritis), K⁺-sparing diuretics, adrenal insufficiency (Addison), ACE inhibitors/ARBs, ↓GFR
Transcellular shift: metabolic acidosis, insulin deficiency, beta-2 blockers

Consequences (cardiac arrhythmias paramount)

Moderate (<8 mM): membrane depolarization, ↑excitability, faster conduction, AP shortening → tall peaked T waves
Severe (>8 mM): Na⁺ channels inactivated → ↓excitability, slower conduction → prolonged PQ, flat P, wide QRS → VT/VF, sinus bradycardia, asystole
Other: RTA type 4, diarrhea/abdominal pain, myalgia, paresthesia, flaccid paralysis, peripheral neuropathy

Hypokalemia ([K⁺] < 3.5 mmol/L)

Causes

Inadequate intake (rare): dementia, starvation, anorexia
Abnormal loss: renal (osmotic diuresis, mineralocorticoid excess, RTA type 1 & 2, K⁺-wasting diuretics), or extra-renal (diarrhea/laxatives directly, vomiting indirectly via metabolic alkalosis)
Transcellular shift into ICF: insulin/beta-2 agonist overdose, SYM overactivation (↑ICP, MI, delirium tremens), metabolic alkalosis

Consequences

Membrane hyperpolarization → ↓excitability, with slower repolarization and prolonged AP. ↓Na⁺/K⁺ ATPase → early after-depolarizations → Torsades de pointes, polymorphic VT, VF
ECG: ST depression, long QT, ↓T amplitude, prominent U wave
Fatigue, weakness, depression, muscle pain/cramps, constipation, bladder atony, depressed reflexes

Treatment of Potassium Disorders

Hyperkalemia: i.v. Ca²⁺ if ECG changes (raises Na⁺-channel threshold), insulin + glucose and inhaled beta-2 agonists (shift K⁺ into cells), diuretics (cautiously), K⁺ exchangers in the gut, and hemodialysis if severe/renal failure
Hypokalemia: oral K⁺ (target ~4 mmol/L), i.v. K⁺ if ECG abnormalities, with monitoring of serum to prevent rebound hyperkalemia

一問一答

▶How does insulin affect potassium?

Insulin drives K⁺ into cells via the Na⁺/K⁺ ATPase (a transcellular shift), helping regulate extracellular K⁺.

▶How is hyperkalemia defined?

Serum [K⁺] > 5.5 mmol/L.

▶How does aldosterone control renal K⁺ excretion?

In the collecting duct it increases ENaC and Na⁺/K⁺ ATPase → Na⁺ reabsorption and K⁺ excretion via ROMK channels.

▶How is body potassium distributed between intracellular and extracellular compartments?

98% is intracellular (~150 mmol/L, critical for protein synthesis); 2% is extracellular (3.5–5 mmol/L), tightly controlled and needed for excitable cells.

▶Why do K⁺ disturbances cause cardiac arrhythmias?

Falling or rising K⁺ hyperpolarizes or depolarizes membranes, altering the excitability of excitable cells including the myocardium.

▶What is the most common cause of hyperkalemia?

Impaired renal excretion (acute & chronic renal failure) — from tubular damage/fibrosis, hyporeninemic hypoaldosteronism, K⁺-sparing diuretics, adrenal insufficiency, ACE inhibitors/ARBs, and ↓GFR.

▶Which transcellular shifts cause hyperkalemia?

Metabolic acidosis, insulin deficiency, and beta-2 blockers (shift K⁺ out of cells).

▶What are the ECG changes of moderate (<8 mM) hyperkalemia?

Membrane depolarization with ↑excitability, faster conduction, and AP shortening → tall, peaked T waves.

▶What are the ECG changes of severe (>8 mM) hyperkalemia?

Na⁺ channels inactivate → ↓excitability, slower conduction → prolonged PQ, flat P, wide QRS → VT/VF, sinus bradycardia, asystole.

▶How is hypokalemia defined?

Serum [K⁺] < 3.5 mmol/L.

▶What are the causes of abnormal K⁺ loss leading to hypokalemia?

Renal: osmotic diuresis, mineralocorticoid excess, RTA types 1 & 2, K⁺-wasting diuretics; extra-renal: diarrhea/laxatives (direct) and vomiting (indirect, via metabolic alkalosis).

▶Which transcellular shifts into cells cause hypokalemia?

Insulin/beta-2 agonist overdose, sympathetic overactivation (↑ICP, MI, delirium tremens), and metabolic alkalosis.

▶What are the ECG changes of hypokalemia?

ST depression, long QT, decreased T amplitude, and a prominent U wave; risk of Torsades de pointes, polymorphic VT, and VF.

▶How does hypokalemia affect membrane excitability?

It hyperpolarizes membranes → ↓excitability, slower repolarization, and prolonged AP; ↓Na⁺/K⁺ ATPase → early after-depolarizations.

▶How is severe hyperkalemia treated?

IV Ca²⁺ if ECG changes (raises Na⁺-channel threshold), insulin + glucose and inhaled beta-2 agonists (shift K⁺ into cells), cautious diuretics, gut K⁺ exchangers, and hemodialysis if severe/renal failure.

▶How is hypokalemia treated?

Oral K⁺ (target ~4 mmol/L); IV K⁺ if ECG abnormalities, with serum monitoring to prevent rebound hyperkalemia.

▶Why does IV calcium help in hyperkalemia with ECG changes?

It raises the Na⁺-channel threshold, stabilizing the myocardial membrane against arrhythmia (it does not lower K⁺ itself).

▶What is hyporeninemic hypoaldosteronism and which conditions cause it?

Low renin/aldosterone causing impaired K⁺ excretion; seen in diabetic nephropathy and lupus nephritis.

▶What non-cardiac consequences can hyperkalemia cause?

RTA type 4, diarrhea/abdominal pain, myalgia, paresthesia, flaccid paralysis, and peripheral neuropathy.

▶What is the aldosterone-independent renal response to K⁺ depletion?

K⁺ depletion activates H⁺/K⁺ ATPase → H⁺ excretion + K⁺ reabsorption, producing a hypokalemic alkalosis.