Proximal tubule reabsorption

PT Anatomy & Function - The Heavy Lifter

• Anatomy & Role: Located in the renal cortex, it's the workhorse for reabsorbing ~65-80% of glomerular filtrate.
• Histology: Lined by simple cuboidal epithelium with a prominent apical brush border (↑ surface area) and packed with mitochondria for ATP-driven transport.
• Key Reabsorption:
  • 100% of glucose & amino acids via secondary active transport (e.g., SGLT2).
  • Most Na⁺, K⁺, Cl⁻, HCO₃⁻, and water. Reabsorption is iso-osmotic.

⭐ The PT has a transport maximum (Tm) for glucose. When plasma glucose exceeds ~200 mg/dL (e.g., diabetes mellitus), SGLT2 transporters are saturated, resulting in glucosuria.

Sodium & Water Reabsorption - The Main Event

• Primary Driver: The basolateral $Na^+/K^+$ ATPase pump actively transports $Na^+$ into the interstitium. This creates a low intracellular $[Na^+]$, establishing the core gradient for reabsorption.
• Apical Transport: $Na^+$ enters the cell from the lumen via:
  • Co-transport: With glucose (SGLT2), amino acids, phosphate.
  • Anti-port: In exchange for $H^+$ (NHE3), facilitating bicarbonate reabsorption.
• Water Reabsorption: Water passively follows solute reabsorption via osmosis, primarily through AQP1 channels (transcellular) and paracellularly. This process is iso-osmotic.

⭐ Exam Favorite: SGLT2 inhibitors (e.g., "-gliflozins") are used in diabetes & heart failure. They block the $Na^+$-glucose cotransporter, causing natriuresis and glucosuria.

Solute Co-transport - Hitching a Ride

The powerful basolateral Na⁺/K⁺ pump establishes a low intracellular [Na⁺], creating the gradient that drives secondary active transport at the apical membrane.

• Glucose & Amino Acids: Fully reabsorbed via apical Na⁺-cotransport (e.g., SGLT2 for glucose). They exit the cell basolaterally via facilitated diffusion (e.g., GLUT transporters).

• Bicarbonate ($HCO_3^−$): ~85% is reclaimed. This process depends on H⁺ secretion (via the Na⁺/H⁺ exchanger, NHE3) and the action of carbonic anhydrase.

• Transport Maximum (Tm): Carrier-mediated transport exhibits saturation. When the filtered load exceeds the reabsorptive capacity, the solute appears in the urine.

  • For glucose, this occurs at plasma levels >200 mg/dL (renal threshold).
  • The maximum reabsorptive rate (Tm) is ~375 mg/min.

⭐ SGLT2 inhibitors (e.g., canagliflozin) are a class of diabetic medications that purposefully induce glucosuria by blocking glucose reabsorption in the proximal tubule, thereby lowering blood sugar.

Tubular Secretion - Taking Out the Trash

• Organic Anion Transporters (OATs): Secrete endogenous waste and exogenous drugs.

  • Endogenous: Urate, bile salts, prostaglandins.
  • Exogenous: PAH (para-aminohippuric acid), penicillin, salicylates, most diuretics (e.g., furosemide).

• Organic Cation Transporters (OCTs):

  • Endogenous: Creatinine, dopamine, epinephrine.
  • Exogenous: Atropine, morphine, metformin.

• Clinical Application:

  • PAH clearance ($C_{PAH}$) approximates renal plasma flow (RPF) because it is both filtered and aggressively secreted.

⭐ Drug Interactions: Probenecid competes with penicillin for the OAT, ↓ its secretion and ↑ its plasma half-life.

High-Yield Points - ⚡ Biggest Takeaways

• The proximal tubule is the workhorse, reabsorbing ~65-80% of water and solutes, including 100% of glucose and amino acids.
• Transport is driven by the basolateral Na⁺/K⁺-ATPase and the entire process is isosmotic.
• Bicarbonate (HCO₃⁻) reabsorption is crucial for acid-base balance and requires carbonic anhydrase.
• PTH inhibits phosphate reabsorption, while Angiotensin II stimulates Na⁺/H₂O reabsorption.
• It is the primary site for secretion of organic anions (PAH) and cations (creatinine).