Tubular Function and Sodium Handling

Tubular Reabsorption and Secretion:

Major mechanisms by which renal tubules modulate the volume and composition of the ultrafiltrate

Serve two major functions

Regulation of urine output and ionic composition
Precise regulation of extracellular fluid volume, osmolarity and pH.

Basic Principles of Renal Epithelial Membrane Transport

Is either protein catalyzed or Bilayer mediated

Naturally permeable or
Ionopore mediated

Is either passive (all 3 types above) or it directly requires energy (pp catalyzed only)

Uniport, symport, or antiport

Electro neutral Vs electogenic

Gibbs-Donnan equilibrium determines electrochemical potential = Driving force in membrane transport

	charge	Na⁺	K⁺	Cl^-	HCO₃^-	Ca⁺⁺
outside cell	+	145 mM	4 mM	116 mM	29 mM	1.8 mM
inside cell	-	12 mM	139 mM	4 mM	12 mM	<0.0002 mM

Modes of Epithelial Transport in the Kidney

Active Transport: energy from ATP, redox; occurs against electrochemical potential gradient. Always uses carrier.

Secondary Active Transport: (cotransport or counter transport) Nrg from linking the downhill movement of one solute (ie Na) to the up hill movement of another.

Passive Diffusion: down hill movement by simple permeation or facilitated transport through pores channels or carriers. H₂O is by passive diffusion in most mammals.

Endocytosis and Exocytosis: requires energy

Solvent Drag: passively carries solute by water flow.

Routes of Epithelial Membrane Transport: Polarized Membranes

Tight Junctions: polarize transporting epithelial cell membrane separating it into apical and basolateral sides and compartmentalizing transporters.

Polarization: is essential for directional transport of solutes (i.e. Na/K ATPase [Na-out] is basolateral only; Na-in transporters are apical [tubular lumen] only] Net Na movement is lumen to pericellular capillaries).

Transcellular transport: occurs in both tubular reabsorption and secretion.

Paracellular transport: occurs across tight junctions in either direction.

General Example of Na Transport

Reabsorption of filtered Na occurs by trans tubular pathway in 2 steps:

(1) Na moves from lumen across apical membrane into cell.

Due to Na’s charge, transporters or channels are required-ie Na/glucose Na/H⁺or Na/Pi exchanger; Na ion pore
Electrochemical gradient of Na is favored so no Nrg is required

(2) Na moves into interstitium and peritubular capillary via basolateral membrane

efflux is uphill so it requires active transport via Na/K-ATPase in basolateral membrane. Has two effects:
(a) intracell Na maintained at 12mM
(b) pump is electrogenic thus maintaining electrical potential of cell

Tubular Reabsorption

99.2% of H2O and 99.4% of Na filtered load are reabsorbed by the renal tubules daily

reabsorption refers to molecules recovered from the ultrafiltrate in tubular lumen: i.e. H₂O, electrolytes (Na, K etc.), aa. Glu etc.

Filtered load = filtered amount of a substance = [substance]_plasma x GFR

Transport Maximum: = maximum amount of a substance that can be reabsorbed per unit time

Results from saturation kinetics; almost all substances have a characteristic Tm due to finite # of transporters
When [solute] exceeds Tm, then solute appears in the urine.

(i.e.: the plasma glucose concentration at which glucose appears in urine = renal threshold for glucose (800mmol/day)

Tubular secretion

Net flux from the pericapillaries to the tubular lumen: regardless of mode of transport, except glomerlular filtration

Both endogenous and exogenous substances (usually weak acids^(-) or bases⁽⁺⁾). Presence of multiple foreign substance transporters may be protective adaptation to potentially toxic substances.

Secreted substances generally fall into the following categories:

Foreign compounds (i.e. drugs)
Paracrine signaling molecules (prostaglandins, etc.) – act at the distal nephron.

Non-metabolized compounds that are excreted unchanged in the urine (i.e. PAH)
Slowly or incompletely metabolized compounds (i.e. Vit B₁₂)
Molecules tightly bound to plasma proteins which can not be efficiently filtered