Renal Tubule Transport – Proximal Convoluted Tubule

Review of Tubular Transport Concepts

• Previous lecture connections
  • Tubular processes divided into reabsorption (lumen → blood) and secretion (blood → lumen).
  • Two anatomical routes for solute or water movement
  • Paracellular: between adjacent tubular cells.
  • Transcellular: across apical membrane → cytosol → basolateral membrane.
  • Two physiological classes of water reabsorption
  • Obligatory: follows solutes automatically; not hormonally regulated.
  • Facultative: hormonally regulated (e.g.
    antidiuretic hormone) and will be addressed in later segments.

Proximal Convoluted Tubule (PCT): Overview

• Handles the largest single fraction of filtrate processing (“lion’s share”).
• Quantitative reabsorption from PCT lumen to peritubular capillaries:
  • \approx 100\% of glucose, amino acids, small peptides/proteins.
  • \approx 65\% of water, Na^+, K^+, Ca^{2+}.
  • \approx 80\% of HCO_3^-.
  • \approx 50\% of Cl^- and urea.
  • Variable fractions of Mg^{2+} and PO_4^{3-}.
• Quantitative secretion from blood → lumen (variable):
  • H^+, urea, NH_4^+, miscellaneous organic acids/bases.
• Energetic principles
  • Primary active transport: direct ATP hydrolysis (e.g.
    Na^+/K^+-ATPase).
  • Secondary (indirect) active transport: uses a pre-existing ion gradient as the energy source (e.g.
    sodium-coupled symporters & antiporters).

Active Reabsorptive Mechanisms in PCT

• Fundamental driver: basolateral Na^+/K^+-ATPase pumps 3\,Na^+ out / 2\,K^+ in, maintaining
  • Low intracellular Na^+ concentration.
  • Negative membrane potential.
• This electrochemical gradient powers multiple apical secondary transporters.

Sodium–Glucose (and Amino Acid) Symport

• Transporter: apical sodium–glucose linked transporter (SGLT); analogous symporters exist for amino acids & small peptides.
• Step-wise events (secondary active):
  1. Binding: Luminal Na^+ (down its gradient) + glucose (against its gradient) simultaneously bind SGLT.
  2. Cotranslocation: Both enter cytosol.
  3. Intracellular handling:
  • Na^+ removed by basolateral Na^+/K^+-ATPase (primary active).
  • Glucose exits basolaterally via facilitated diffusion (GLUT transporter) → interstitium → peritubular capillary.
• Energetics shorthand
  • Overall process = secondary active (indirect) because ATP is consumed only at the Na^+/K^+ pump stage.
• Health implication: virtually 100\% tubular reabsorption keeps plasma glucose nil in urine.
  • Glycosuria appears only when plasma glucose exceeds renal transport maximum (e.g.
    diabetes mellitus).

Sodium Reabsorption & Hydrogen Secretion (Na⁺/H⁺ Antiporter)

• Transporter: apical Na^+/H^+ exchanger (NHE).
• Source of H^+:
  • CO2 diffuses into PCT cell → combines with H2O via carbonic anhydrase to form H2CO3 → dissociates into HCO_3^- + H^+.
• Step-wise events:
  1. Apical NHE moves Na^+ into cell (down gradient) while secreting H^+ into lumen (against gradient).
  2. Basolateral Na^+/K^+-ATPase expels intracellular Na^+ to sustain gradient.
• Functional significance
  • Prevents systemic acidosis by secreting excess H^+.
  • Couples to downstream bicarbonate reclamation (next section).

Bicarbonate Reabsorption Cycle

• In-lumen chemistry (driven by secreted H^+):
  
  H^+{(lumen)} + HCO3^-{(lumen)} \longrightarrow H2CO3 \longrightarrow CO2 + H_2O
  
• CO2 diffuses back into cell, repeats hydration reaction, generating new intracellular HCO3^-.
• When intracellular [HCO3^-] rises sufficiently → basolateral facilitated diffusion (electrogenic HCO3^- transporter) moves bicarbonate into interstitium → blood.
• Net results per cycle
  • One filtered HCO_3^- reclaimed.
  • One H^+ recycled (not excreted, hence process can iterate many times along PCT).
• Physiological importance
  • Roughly 80\% of total filtered bicarbonate is rescued here.
  • Maintains blood buffer capacity for H^+ produced in metabolism & respiration.

Passive Reabsorption & Water Movement

• Spatial distinction within PCT
  • Early (first half): intense active uptake of solutes (SGLT, NHE, amino acid cotransport).
  • Late (second half): passive, gradient-driven recovery of additional solutes.
• Osmotic events
  1. Early active solute reabsorption ↑ osmolarity of peritubular capillary blood.
  2. Creates osmotic gradient → obligatory water reabsorption from lumen to blood.
  • Via paracellular pathway (tight junction leakiness) and transcellular pathway (aquaporin-1 water channels on both apical & basolateral membranes).
  1. Removal of water concentrates remaining luminal solutes (e.g.
     Cl^-, K^+, Ca^{2+}, urea).
  2. Concentrated solutes now diffuse passively (paracellular &/or transcellular) into interstitium following their electrochemical gradients.
• No direct ATP usage (truly passive).

Summary of Quantitative Reabsorption/Secretion in PCT

• Reabsorbed (approximate fractions of filtered load)
  • 100\%: glucose, amino acids, small proteins/peptides.
  • 80\%: HCO_3^-.
  • 65\%: water, Na^+, K^+, Ca^{2+}.
  • 50\%: Cl^-, urea.
  • Variable: Mg^{2+}, PO_4^{3-}.
• Secreted (variable amounts)
  • H^+ (acid–base balance).
  • Urea (fine-tunes nitrogen disposal).
  • NH_4^+ (ammoniagenesis, contributes to urinary buffering).

Clinical/Physiological Significance & Exam Tips

• Acid–Base Role: PCT bicarbonate reclamation is the primary defense against metabolic acidosis.
• Transport Saturation: SGLT reaches a transport maximum (Tm). Exceeding Tm produces glucose in urine (diagnostic for diabetes mellitus or renal threshold defects).
• Proteinuria: Trace proteins may appear normally, but persistent/profound proteinuria implies glomerular damage, not PCT malfunction.
• Pharmacology parallels (preview; not directly in transcript but conceptually linked)
  • Carbonic anhydrase inhibitors (e.g.
    acetazolamide) block bicarbonate reabsorption → therapeutic diuresis in certain conditions.
• Exam strategy
  • Be able to sketch or narrate one entire transporter system (e.g.
    SGLT or NHE) including ion directions, energy source, and physiological purpose.
  • Remember the difference between primary vs secondary active transport and between obligatory vs facultative water reabsorption.
  • Quantitative fractions (65 %, 80 %, 100 %) are high-yield memory anchors for
    PCT function.