11 - Proximal Tubule Reabsorption and Secretion

proximal tubule

first segment of nephron where bulk of reabsorption occurs

• 65% of water and solutes reabsorbed, 117L of water reabsorbed

• contains microvilli that enhances surface area of proximal tubule for reabsorption

• contains lots of mitochondria to power reabsorption

• leaky tight junctions allow paracellular diffusion

• in contact with peritubular capillaries → efficient solute transfer

reabsorption of substances

some solutes reabsorbed more avidly than others because of the presence of transporters specific to certain solutes in nephron

• glucose and amino acids completely reabsorbed

• 80% of bicarbonate is reabsorbed

• inulin → amount of inulin within PT stays the same but filtrate concentration increases since water is reabsorbed

  • if there is more solute left in proximal tubule than inulin → secreted

  • if there is less solute left in proximal tubule than inulin → reabsorbed

transcellular vs paracellular reabsorption

• transcellular → requires transporters or channels on apical or basolateral membranes

  • primary active, secondary active, passive diffusion

• paracellular → driven by concentration gradients and leaky tight junctions

proximal tubule reabsorption and secretion

• reabsorption → Na⁺, water, HCO₃^-, amino acids, glucose

• secretion → drugs

Na⁺ transport in proximal tubule

Na⁺ is reabsorbed from proximal tubule

• Na⁺ enters cell from lumen down its concentration gradient (apical)

  • co-transport with phosphate, glucose, or amino acids

  • Na⁺/H⁺ exchanger → counter-transporter

• Na⁺ exits cell into blood against its concentration gradient (basolateral)

  • Na⁺/K⁺-ATPase → pumps 3 Na⁺ out and 2 K⁺ in, establishes Na⁺ gradient

water transport in proximal tubule

as Na⁺ is reabsorbed, water follows

• 75% of water reabsorbed trancellularly through aquaporin 1 (apical/basolateral)

• 25% of water reabsorbed paracellularly through tight junctions

HCO₃^- transport in proximal tubule

80% of HCO₃^- is reabsorbed from proximal tubule, with carbonic anhydrase playing a key role in reabsorption

• in the lumen (apical)

  • H⁺ is pulled out of cell via Na⁺/H⁺ exchanger and H⁺-ATPase

  • H⁺ combines with HCO₃^- to form H₂CO₃

  • H₂CO₃ converts to water and CO₂ via carbonic anhydrase 4 and 14

  • water and CO₂ passively diffuse into cell

• in proximal tubule cell

  • water and CO₂ combine via carbonic anhydrase 2 to form H₂CO₃

  • H₂CO₃ breaks down into H⁺ and HCO₃^-

• in the blood (basolateral)

  • HCO₃^- is transported into cell via Na⁺ co-transporter or Cl^- counter-transporter

amino acid transport in proximal tubule

filtered small proteins get broken down by proteases in proximal tubule brush border or endocytosed and hydrolyzed by peptidases

• amino acids are reabsorbed by a variety of transporters, specific for each amino acid (apical/basolateral)

drug transport in proximal tubule

penicillin, drugs, and diuretics are secreted by a variety of transporters (apical/basolateral)

glucose transport in proximal tubule

glucose is reabsorbed from proximal tubule

• SGLT1/2 → glucose co-transporter with Na⁺ from lumen into cell (apical)

  • secondary active transport due to high glucose concentrations in cell

  • can become saturated and rate-limiting

• GLUT1/2 → facilitated diffusion of glucose from cell to blood (basolateral)

  • Na⁺ pumped into blood via Na⁺/K⁺-ATPase

glucose reabsorption and secretion

as plasma glucose concentration increases, amount of glucose in tubular lumen (filtrate) increases → filtered load = [plasma] x GFR_inulin

• reabsorbed → maximum glucose transport from lumen into cell

  • SGLT1/2 become saturated

  • Tm_glucose = 375 mg/min

• excreted → glucose spills into urine and is excreted since transporters or filtered

  • threshold = 300 mg/dL

• splay: curve in reabsorption and secretion lines between threshold and T_m

  • reflects anatomical and kinetic differences in nephron, variation among nephron transport capacity

• increased glucose in filtrate causes osmotic diuresis and increases urine output