Renal Physiology: Tubular Transport and Urine Formation covers renal tubular transport and urine formation for INI CET (AIIMS PG).
Tubular Reabsorption and Secretion:
Proximal Tubule (~65-70% of filtered load reabsorbed):
- Na⁺ reabsorption: Na⁺/K⁺-ATPase at basolateral membrane → creates gradient → Na⁺ enters via Na⁺/H⁺ exchanger (NHE3) + other cotransporters
- Glucose reabsorption: SGLT2 (Na⁺-glucose cotransporter — high capacity, low affinity) at luminal membrane of early PT; SGLT1 in late PT; virtually all filtered glucose is reabsorbed under normal conditions
- Renal threshold for glucose: ~180 mg/dL — when blood glucose exceeds this, glucose appears in urine
- Amino acid reabsorption: Na⁺-dependent cotransporters (specific for neutral, acidic, basic amino acids)
- Bicarbonate reabsorption: ~85-90%; H⁺ secreted via NHE3 → H₂CO₃ → CO₂ + H₂O (catalyzed by CA IV on brush border) → CO₂ diffuses back → HCO₃⁻ reabsorbed
- Water reabsorption: Obligatory (isotonic) — follows Na⁺; AQP1 channels in PT and descending limb
- Secretion: Organic anion/cation transporters (PAH — para-aminohippuric acid; uric acid; drugs — penicillin, salicylates)
Loop of Henle (Countercurrent system — critical for concentrating urine):
- Descending limb: Thin; highly permeable to water (AQP1); impermeable to solutes → water leaves → fluid becomes hypertonic (up to 1200 mOsm/kg at papilla)
- Thick ascending limb (TAL): Impermeable to water; Na⁺/K⁺/2Cl⁻ cotransporter (NKCC2) → active reabsorption of these ions (furosemide blocks NKCC2); generates the medullary osmotic gradient (countercurrent multiplication)
- Liddle’s syndrome: Gain-of-function mutation in ENaC → ↑Na⁺ reabsorption → hypertension
- Diluting segment: Fluid entering DCT is hypotonic (~100 mOsm/kg); TAL actively reabsorbs NaCl but not water → further dilution to ~50-100 mOsm/kg
Distal Tubule and Collecting Duct:
- Early DCT: Na⁺/Cl⁻ cotransporter (NCC) — thiazides inhibit NCC
- Late DCT + Collecting duct: Principal cells (Na⁺ reabsorption via ENaC, K⁺ secretion) and Intercalated cells (H⁺/K⁺-ATPase, H⁺-ATPase — acid secretion)
- Aldosterone: Binds mineralocorticoid receptors in principal cells → ↑ENaC synthesis + ↑Na⁺/K⁺-ATPase → Na⁺ reabsorption + K⁺ secretion
- ADH (Vasopressin): Binds V2 receptors on collecting duct → ↑AQP2 water channels in apical membrane → water reabsorption → concentrated urine
Countercurrent Multiplication System:
- Countercurrent flow: Descending limb (water out) + Ascending limb (solutes in, water not) → creates medullary concentration gradient
- Vasa recta: Peritubular capillaries arranged in hairpin loops → preserve the gradient (slow blood flow prevents washout)
- Final urine concentration: Up to 4-5× plasma osmolality (max 900-1200 mOsm/kg with max ADH)
- Free water clearance (C_H₂O): V – (U Osm × V / P Osm) — positive = dilute urine; negative = concentrated urine
Acid-Base Regulation:
- Daily H⁺ production: ~50-100 mEq (from metabolism of sulfur-containing amino acids, phosphoproteins)
- Buffer systems: Bicarbonate buffer (most important extracellular), Proteins, Hemoglobin, Phosphate, Ammonium (NH₄⁺) — key adaptive mechanism
- Renal H⁺ handling:
- Reabsorption of filtered HCO₃⁻ (proximal tubule)
- Excretion of titratable acid (TA — H⁺ buffered by HPO₄²⁻ → H₂PO₄⁻)
- Excretion of NH₄⁺ (critical for acid excretion — glutamine metabolism → NH₃ + HCO₃⁻ → NH₄⁺ excreted + HCO₃⁻ generated)
⚡ Exam Tip for INI CET (AIIMS PG): Loop diuretics (furosemide) block NKCC2 in TAL → ↓NaCl reabsorption → ↓medullary gradient → ↓water reabsorption → hypokalemia (volume depletion → secondary hyperaldosteronism → K⁺ loss) + metabolic alkalosis (contraction alkalosis; also ↑H⁺ excretion). Thiazides (HCTZ) block NCC in DCT → similar hypokalemia + metabolic alkalosis.