Renal Potassium Balance

What are the roles of intracellular and extracellular potassium?

• Intracellular K⁺:

  • Maintains cell volume (osmotic balance).

  • Regulates intracellular pH.

  • Supports enzyme activity and protein/DNA synthesis.

• Extracellular K⁺:

  • Ratio [K⁺]in/[K⁺]out sets resting membrane potential.

  • Controls neuromuscular excitability.

  • Essential for cardiac conduction and rhythm.

  • Influences vascular tone (low K⁺ → vasoconstriction; high K⁺ → vasodilation).

How is potassium homeostasis maintained after a meal?

• Normal meal: ~33 mEq K⁺.

• Without regulation: ECF [K⁺] ↑ by ~2.4 mEq/L (potentially lethal).

• Rapid cellular uptake: shifts K⁺ into cells within minutes.

• Renal excretion: slower (hours), maintains long‑term balance.

What are physiologic roles and causes of imbalance?

• Distribution: ~50 mEq/kg; 98% ICF (~146 mEq/L), 2% ECF (3.5–5.0 mEq/L).

• Physiologic role: maintains membrane potential, regulates excitability, supports muscle contractility.

• Hypokalemia causes: diuretics, vomiting, genetic defects in Na⁺/Cl⁻ symporters.

• Hyperkalemia causes: renal failure, ACE inhibitors, K⁺‑sparing diuretics, supplements.

• Modulating factors:

  • Acidosis: ↑ plasma K⁺.

  • Alkalosis: ↓ plasma K⁺.

  • ↑ osmolality, cell lysis, exercise → ↑ plasma K⁺.

What transporters and hormones regulate K⁺ uptake into cells?

• Transporters:

  • Na⁺/K⁺ ATPase (Na⁺ out, K⁺ in).

  • NKCC (Na⁺‑K⁺‑2Cl⁻ cotransporter).

• Hormones:

  • Insulin: stimulates Na⁺/K⁺ ATPase, GLUT4.

  • Catecholamines: β₂‑AR ↑ cAMP → ↑ K⁺ uptake; α‑AR inhibits insulin.

  • Aldosterone: ↑ Na⁺/K⁺ ATPase expression.

• Systemic coordination: pancreas (insulin), adrenal cortex (aldosterone), adrenal medulla (epinephrine).

How does acidosis affect K⁺ transport?

• ↑ H⁺ displaces K⁺ from cells → efflux.

• Low pH inhibits Na⁺/H⁺ exchange and Na⁺/HCO₃⁻ cotransport → ↓ Na⁺ entry.

• ↓ Na⁺ + high H⁺ → inhibit Na⁺/K⁺ ATPase and NKCC → ↓ K⁺ uptake.

• Net effect: hyperkalemia.

How does dietary intake affect K⁺ excretion?

• Depletion: ~0–2% excretion.

• Normal intake: 15–80%.

• High intake: up to 150% of filtered load.

• Site: principal cells in DT & CCD secrete K⁺.

How much K⁺ is reabsorbed in PT and TAL?

• PT: ~67%.

• TAL: ~20%.

• Constant fraction reabsorbed under most conditions.

How do α‑intercalated and principal cells handle K⁺?

• α‑intercalated cells: reabsorb K⁺ (low K⁺ diet), secrete H⁺ (H⁺‑ATPase, K⁺/H⁺ ATPase).

• Principal cells: secrete K⁺; secretion depends on Na⁺ delivery → electrochemical gradient.

• Transporters: K⁺/Cl⁻ symporter, ROMK, BK channels.

What factors regulate K⁺ secretion in DT/CCD?

• Na⁺/K⁺ ATPase: maintains intracellular K⁺, drives gradient.

• Electrochemical gradient: drives K⁺ efflux via ROMK/BK.

• Regulators:

  • Plasma K⁺ ↑ → ↑ secretion.

  • Aldosterone → ↑ Na⁺ reabsorption, ↑ K⁺ secretion.

  • Ang II → inhibits ROMK → ↓ secretion.

  • AVP → modulates water/electrolytes.

  • Flow rate ↑ → ↑ secretion (diuretics, osmotic load).

  • Acid‑base disorders.

How does arginine vasopressin (AVP) affect K⁺ secretion in the distal tubule and collecting duct?

• Stimulates secretion:

  • ↑ Na⁺ conductance → depolarizes apical membrane → ↑ driving force for K⁺ efflux.

  • ↑ apical K⁺ permeability → ↑ K⁺ secretion.

• Inhibits secretion:

  • ↓ tubular fluid flow → ↓ K⁺ secretion.

• Net effect: No overall change in urinary K⁺ excretion (balance of stimulation and inhibition).

How does metabolic acidosis affect K⁺ secretion?

• Acute acidosis: ↓ K⁺ secretion → ↓ urinary K⁺ excretion.

  • Mechanism: ↓ Na⁺/K⁺ ATPase activity, ↓ apical K⁺ permeability in DT/CCD.

• Chronic acidosis: ↑ K⁺ secretion → ↑ urinary K⁺ excretion.

  • Mechanism: hyperkalemia → ↑ aldosterone secretion → stimulates distal K⁺ secretion.

What are the major regulators of distal K⁺ secretion?

• Plasma K⁺ concentration: direct stimulus.

• Aldosterone: enhances Na⁺ reabsorption and K⁺ secretion.

• Tubular flow rate: high flow → BK channel activation → ↑ secretion.

• AVP: modulates secretion indirectly.

• Acid‑base status: acute acidosis ↓ secretion; chronic acidosis ↑ secretion.

How do systemic and renal mechanisms integrate to regulate K⁺ balance?

• Systemic: hormones (insulin, catecholamines, aldosterone) shift K⁺ into cells.

• Renal: distal nephron is final checkpoint for excretion.

• Disorders (hypo/hyperkalemia) often reflect combined systemic + renal dysfunction.

What factors influence K⁺ secretion by principal cells?

• Na⁺ delivery: more Na⁺ → stronger gradient → ↑ K⁺ secretion.

• Aldosterone: ↑ Na⁺/K⁺ ATPase, ENaC, ROMK.

• Flow rate: ↑ flow → BK channel activation.

• AVP: mixed effects, net balance.

• Acid‑base status: acidosis vs alkalosis.

• Ang II: inhibits ROMK → ↓ secretion.

How do opposing factors interact to regulate K⁺ secretion?

• Acidosis: ↓ Na⁺/K⁺ ATPase, ↓ K⁺ secretion despite ↑ distal flow.

• Volume expansion: ↑ distal flow but ↓ aldosterone → variable effect.

• Water diuresis: ↓ AVP but ↑ distal flow → ↑ K⁺ secretion.

• Volume contraction: ↑ aldosterone but ↓ distal flow → balance determines outcome.

What is the most immediate response to a meal (ingested K⁺)?

↑ intracellular K⁺ in skeletal muscle (rapid uptake).

Which ion channel is directly opened by increased tubular flow rate?

BK channel.

What is the effect of angiotensin II on K⁺ secretion?

Decreases secretion (inhibits ROMK).

What is the effect of AVP on K⁺ secretion by DT and CD?

Net effect: No overall change (stimulates secretion but reduces flow).

↑ secretion per cell × ↓ flow = ~ no net change in total K⁺ excretion

How does a high K⁺ diet affect urinary K⁺ excretion?

• Primary site: late distal tubule (DT) and cortical collecting duct (CCD).

• Mechanism:

  • ↑ Na⁺ reabsorption → stronger electrochemical gradient → drives K⁺ secretion.

  • High plasma K⁺ → ↑ aldosterone → ↑ Na⁺/K⁺ ATPase, ↑ ENaC, ↑ K⁺ channels.

• Supporting role: PT, TAL, DT reduce Na⁺ reabsorption → more Na⁺ delivered distally.

• Chronic high intake: ↓ Na⁺/H⁺ exchanger (PT/TAL), ↓ NKCC (TAL), ↓ Na⁺/Cl⁻ symporter (DT).

How do aldosterone and flow rate regulate K⁺ secretion?

• Aldosterone:

  • ↑ Na⁺/K⁺ ATPase activity.

  • ↑ ENaC channels.

  • ↑ ROMK channels.

• High flow rate:

  • Detected by cilia on principal cells.

  • ↑ intracellular Ca²⁺ → opens BK channels.

  • Net effect: ↑ K⁺ secretion.

What is the effect of AVP on K⁺ secretion in DT and CD?

• Stimulates secretion: ↑ Na⁺ conductance, ↑ apical K⁺ permeability.

• Inhibits secretion: ↓ tubular fluid flow.

• Net effect: Constant K⁺ balance (no overall change in urinary K⁺ excretion).

How does acidosis affect K⁺ secretion?

• Acute acidosis: ↓ Na⁺/K⁺ ATPase, ↓ apical K⁺ permeability → ↓ K⁺ secretion.

• Chronic acidosis: hyperkalemia → ↑ aldosterone → ↑ K⁺ secretion.

• Net effect: acute ↓ secretion, chronic ↑ secretion.

What are the key regulators of distal K⁺ secretion?

• Plasma K⁺ concentration: direct stimulus.

• Aldosterone: enhances Na⁺ reabsorption, ↑ K⁺ secretion.

• Tubular flow: high flow → BK channel activation.

• AVP: mixed effects, net balance.

• Acid‑base status: acute acidosis ↓ secretion; chronic acidosis ↑ secretion.

How do systemic and renal mechanisms integrate to regulate K⁺ balance?

• Systemic: insulin, catecholamines, aldosterone shift K⁺ into cells.

• Renal: distal nephron is final checkpoint for excretion.

• Disorders (hypo/hyperkalemia) reflect combined systemic + renal dysfunction.

How do opposing factors interact in K⁺ secretion?

• Acidosis: ↓ Na⁺/K⁺ ATPase → ↓ secretion despite ↑ distal flow.

• Volume expansion: ↑ distal flow but ↓ aldosterone → variable effect.

• Water diuresis: ↓ AVP but ↑ distal flow → ↑ secretion.

• Volume contraction: ↑ aldosterone but ↓ distal flow → balance determines outcome.