Renal Tubular Physiology — Potassium Handling

Potassium

• Predominany intracellular cation
• Total Stores: Approx 3200mmol (50mmol/kg)
• Key Functions:
  • Main determinant of ICF osmolality and tonicity
  • Responsible for RMP of excitable cells via Goldmann-Hodgkin-Katz due to ↑↑gK relative to other species
  • Role in action potential → repolarisation phase
  • Secretion of insulin and multiple other KATP dependant processes
  • Regulation of IC processes (protein/glycogen synthesis)
  • Involved in Na+/K+ ATPase in cell membranes

Potassium Elimination

• Faecal – 8mmol/day
• Renal – 92mmol/day (See next heading for details)
  • Urinary K+ excretion = [K+ filtered by glomerulus] + [K+ secreted by CCD/LDCT] – [K+ reabsorbed by renal tubules]
  • Glomerular filtration: Freely filtered = 756mmol/day (180L x 4.2mmol/L)
  • PCT: 65% reabsorption
  • LoH: 25~30% reabsorption
  • DCT/Collecting Ducts – variable
    • Determined by Aldosterone, Plasma [K+], Tubular Flow rate
    • Secreted by principal cells
    • Reabsorbed by intercalating cells

K+ handling within the tubular system:

• PCT (55% of filtered K+ is reabsorbed):
  • K+ is reabsorbed passively via the paracellular route due to:
    • Solvent drag → coupled to flow of Na+ and H2O
    • [ ] gradient → created by reabsorption of H2O
    • Electrical gradient → due to +ve luminal charge in late PCT
• TAL of LoH (30% of filtered K+ is reabsorbed):
  • K+ is reabsorbed by 2° active transport via paracellular route → +ve charged lumen generated by ion flux created by NKCCT transporter causes K+ to be reabsorbed by diffusion down its electrical gradient
• LDCT and CCD (0 to > 15% K+ is secreted):
  • Principal cells of CCD and LDCT → 2° active secretion K+ → via:
    • Basolateral Na+ /K+ ATPase → (i) generates an electrochemical gradient that draws Na+ intracellularly from the tubular lumen (via the ENaC channel), and (ii) pumps K+ from peritubular capillaries into tubular cell
    • The –vely charged lumen generated by influx of Na+ across ENaC channel → favours tubular secretion of K+
  • o Type A intercalated cells of CCD and LDCT → 2° active reabsorption of K+ :
    • H+ is produced within tubular cell by hydration of CO2 (using CA) → H+ is then exchanged for tubular K+
• MCD (5% of filtered K+ is reabsorbed)

Renal K⁺ regulation:

• Renal K+ regulation occurs MAINLY via control of K+ secretion at the distal nephron (CCD and LDCT) via the following factors:
  • Circulating factors:
    • Plasma [K+ ]
      • ↑ [K+ ] causes ↑ K+ secretion by → (i) Directly stimulating Na+ /K+ ATPase in principal cells, and (ii) Directly stimulating Aldosterone release from adrenal cortex
    • Aldosterone
      • ↑ aldosterone causes ↑ K+ secretion by → ↑ production of Na+ /K+ ATPase, K+ channels and ENaC Na+ channels in the principal cells
    • Plasma pH
      • Alkalosis via ↓ plasma [H+ ] causes ↑ K+ secretion by → stimulating Na+ /K+ ATPase in principal cells
  • Luminal factors:
    • Flow of tubular fluid in DCT and CCD
      • ↑ tubular fluid flow causes ↑ K+ secretion by → maintaining ↓ luminal [K+ ] (Ie. continuously washing it away) → permits passive diffusion of K+ ↓ its [ ] gradient into tubular lumen
    • ↑ Na+ delivery rate to DCT and CCD → ↑ K+ secretion
    • -ve lumen potential difference → ↑ K+ secretion

JC / Gladwin / Sakurai / Bianca 2020

Answer by Bianca, Gladwin, JC, Sakurai