PROXIMAL TUBULE TRANSPORT

A. Role: Initial adjustment of tubular fluid by reabsorption (main mechanism) and by secretion

Reabsorption: Transport from tubular lumen to peritubular capillary blood
Secretion: Transport from peritubular capillary blood into the tubular lumen

B. Active Reabsorption (direct active transport and cotransport - secondary active transport, symport)

1. Based on Na+ active transport (actually Na-K-ATPase) pump at the interstitial (baso-lateral) cell membrane (leading to low intracellular Na+), and carrier-mediated cotransport at the luminal (apical) membrane powered by the Na+ luminal-intracellular concentration gradient

2. Substances actively reabsorbed (mainly transcellular)

Sodium ion	about 70% (60-80%, including passive component)
Chloride ion	about 70% (60-80%, including passive component)
Glucose	complete
Amino acids	complete
Plasma proteins	complete (only small amount filtered)

C. Passive Reabsorption: due to concentrating effect of active reabsorption followed by water reabsorption plus solvent drag

Sodium ion	paracellular
Chloride ion	paracellular
Bicarbonate ion	variable (depends in part on H+ secretion)
Potassium ion	most or all
Urea	about 40% (because of low permeability)
Water	about 70% (60-80%) (due to osmotic effect of particle reabsorption)

Mechanism:

Active particle reabsorption (particularly Na⁺) creates a small osmotic gradient between the luminal fluid and the spaces between tubule cells on the interstitial surface.

The osmotic gradient causes water to be reabsorbed because the proximal tubule is very permeable to water.

The water reabsorption concentrates the remaining dissolved substances (including Na⁺), and, if they are readily permeable, the resulting concentration gradient leads to their reabsorption at about the same rate as water.

Note: The above mechanism maintains proximal tubule fluid approximately iso-osmotic with plasma

Note:  About two-thirds of the water and filtered particles are reabsorbed in the proximal tubule.  If the GFR is reduced, reabsorption is reduced in proprotion;  if GFR increases, reabsorption increases in proportion.  This is termed Glomerular-Tubular Balance.

D. Active Secretion

1. Mechanism: cotransport with Na⁺ ion reabsorption (antiport)

2. Substances secreted, e.g.

Exogenous
Para-aminohippurate (PAH)
Iodinated dyes (e.g., Diodrast)
Certain pharmacological agents (e.g. penicillin, note effect of probenecid)

Endogenous
Hydrogen ion (Na⁺ antiport)

E. No Transport

1. Not actively transported and tubule impermeable to diffusion

Inulin (exogenous indicator)
Creatinine (endogenous protein metabolism product)

Summary

Entering the proximal tubule at a rate of about 120 ml/min is an ultrafiltrate of blood plasma.

As a direct or indirect consequence of active transport, about 70% of the amount filtered is reabsorbed and returned to the body by way of the peritubular capillaries and renal veins.

Since the proximal tubule is quite permeable to water, the tubular fluid remains iso-osmotic to plasma, but its composition is changed (e.g. no glucose, higher urea and creatinine concentrations, about the same sodium and chloride concentrations).

The remaining fluid leaves the proximal tubule and enters the loop of Henle at a rate of about 30-35 ml/min.

F. Tubular Transport Maximum [T_m] (applies to all tubule segments, not just the proximal tubule)

For many substances transported by carriers (active transport or facilitated diffusion), there exists some maximum rate for their transport; this is termed their tubular transport maximum or T_m

When the quantity of a substance presented for transport is greater than the T_m for that substance, the excess is not transported and is either excreted (for reabsorbed substances) or returned to the body in the renal venous blood (for secreted stubstances)

Examples:

Glucosuria in diabetes mellitus (note: P_Glucose = plasma glucose concentration)
Albuminurea in nephritis