Renal Physiology – Tubular Reabsorption & Secretion Vocabulary

Recap & Context

• Lecture continues renal physiology following discussion of filtration.
• Prior session covered:
  • Location: renal corpuscle.
  • Filtration membrane composition.
  • Net Filtration Pressure (NFP) concept and calculation.
  • Glomerular Filtration Rate (GFR) regulation:
  • Autoregulation.
  • Neural (sympathetic).
  • Hormonal (Angiotensin II & Atrial Natriuretic Peptide).
• Current focus: Tubular Reabsorption & Secretion (second and third basic renal processes).

Terminology

• Filtrate = fluid in glomerular capsule.
• Tubular fluid = same fluid once it enters renal tubule.
• Although named differently, they contain identical components.

Tubular Reabsorption

• Direction: from tubular fluid → blood (peritubular capillaries / vasa recta).
• Purpose: reclaim vital substances filtered at glomerulus.
• Quantitative dominance: Majority occurs in proximal convoluted tubule (PCT); later segments & collecting duct fine-tune reabsorption for homeostasis.
• Substances reabsorbed (nearly completely unless pathologic):
  • Water.
  • Glucose.
  • Proteins & small peptides (via vesicular endocytosis).
  • Urea (≈50 % reabsorbed).
  • Ions: Na^+,\;K^+,\;Ca^{2+},\;Cl^-,\;HPO4^{2-},\;HCO3^-.
• Rationale: without reabsorption, blood viscosity would skyrocket and essential solutes would be lost.

Tubular Secretion

• Direction: blood, interstitial fluid, or tubule cells → tubular fluid.
• Everything secreted is destined for excretion in urine.
• Occurs along entire nephron & collecting duct.
• Key secreted items:
  • Ions: H^+,\;K^+,\;NH_4^+.
  • Creatinine (100 % secreted in healthy adults).
  • Drugs / xenobiotics (e.g. steroids, erythropoietin abuse detection, GH, cocaine, marijuana).
• Physiological outcomes:
  1. Acid–base balance – secretion of H^+ helps regulate blood pH.
  2. Potassium homeostasis – prevents hyperkalemia (dangerously high K^+).
  3. Removal of toxins & drug metabolites.
• Diagnostic link: urinalysis reveals disease (e.g. proteinuria, glucosuria) and doping.

Global Mass Balance (per 180 L/day GFR)

Routes of Solute & Water Movement

1. Paracellular pathway
   • Between adjacent tubule cells.
   • Cells joined apically by tight junctions (seal at lumen side).
   • Purely passive diffusion down concentration or electrochemical gradients.
2. Transcellular pathway
   • Through the cell: crosses apical membrane → cytosol → basolateral membrane → interstitial fluid → blood.
   • Requires membrane transport proteins.

Membrane Domains

• Apical (luminal) membrane: faces tubular fluid.
• Basolateral membrane: faces interstitial fluid & peritubular capillaries.

Transport Mechanisms (Transcellular)

• Passive (down gradient):
  • Simple diffusion.
  • Facilitated diffusion via channels/Carriers (e.g. ion channels, aquaporins for water).
• Active (against gradient):
  1. Primary Active Transport
  • Direct ATP use (e.g. Na^+ / K^+-ATPase).
  1. Secondary Active Transport
  • Leverages energy of one solute moving with its gradient to move another against its gradient.
  • Symporters (cotransport, both same direction).
  • Antiporters (counter-transport, opposite directions).

Transport Maximum (T_{max})

• Analogous to elevator capacity analogy.
• Definition: upper limit ( mg min⁻¹) of solute that transporter system can move.
• Once saturated, additional solute remains in tubular fluid → excreted (clinical relevance: glucose in diabetes).

Water Reabsorption

All water movement is passive osmosis driven by solute reabsorption.

1. Obligatory Water Reabsorption

• ~80 % of total water reabsorbed.
• Coupled directly to solute (mostly Na^+, also K^+, glucose) uptake.
• Locations:
  • Proximal convoluted tubule.
  • Descending limb of nephron loop.
• Tubule walls here are always water-permeable.
• Does not change osmolarity of blood or interstitial fluid (water follows solute proportionally).

2. Facultative Water Reabsorption

• Remaining ~20 % of water.
• "Facultative" = adaptable to need.
• Regulated by Antidiuretic Hormone (ADH).
• Locations: late distal convoluted tubule & collecting duct.
• When ADH inserts aquaporins, additional water reabsorbs → decreases osmolarity of blood/interstitial fluid (dilutes solute).

Clinical / Practical Connections

• Hyperkalemia avoidance via K^+ secretion – critical because potassium disturbances are the most acutely fatal electrolyte disorders.
• pH regulation via H^+ secretion – one of the primary long-term acid–base buffering systems.
• Creatinine clearance – because creatinine is completely secreted, its urinary concentration is a key diagnostic for GFR estimation.
• Urinalysis – screens for:
  • Pathologies (proteinuria, glycosuria).
  • Doping agents (steroids, EPO, GH, recreational drugs).

High-Yield Takeaways

• Reabsorption = reclaim; secretion = destined for excretion.
• ~180 L/day filtered, but <1 % excreted → underscores efficiency of tubular processes.
• Two anatomical pathways (para- vs transcellular) and multiple transport modes (passive, primary & secondary active).
• T_{max} saturation concept explains renal thresholds for glucose, amino acids, etc.
• Water reabsorption split into obligatory (solute-linked, PCT + loop) and facultative (ADH-regulated, DCT + CD).