Proximal Tubule

Created by Hosworth 

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Patterns of reabsorption

1. Obligatory - Proximal tubule
2. Facultative - Distal nephron

Obligatory - Proximal tubule

Approximately 2/3 of the filtered solute and H2O are reabsorbed in the proximal
tubule in a fixed ratio. This is, water and solute are reabsorbed in a fixed pattern due
to the obligatory coupling of H2O flow to solute flow in this segment of the nephron.

Facultative - Distal nephron

Solute and H2O reabsorption are regulated independently (to a large extent) and are
not obligatorily coupled in this segment of the nephron. The distal nephron
(including the collecting duct) provides the "fine tubing" of fluid and electrolyte
regulation.

Reabsorption of sodium chloride and water by the proximal tubule

The mechanisms of tubular function have been studied using a variety of techniques. Two of
the more important techniques are illustrated below

Mechanisms of fluid and electrolyte reabsorption along the length of the proximal tubule-
isosmotic reabsorption

Using micropuncture analysis of solute and osmolar concentrations to
indicate function. Changes in the inulin
concentration (trace quantities)
and osmolality of the tubular
fluid (TF) relative to that of
plasma (P) along the length of
the proximal tubule. Since the
concentration of inulin, a
nonreabsorbable solute,
increases by approximately
3-fold at the end of the
proximal tubule, but without a
change in tubular fluid
osmolarity, the proximal
tubule must have isomotically
reabsorbed two-thirds of the
filtered fluid.

Changes in the Na+, Cl-, and HCO3- concentrations of the tubular fluid (TF)
relative to that of plasma (P) along the length of the proximal tubule

Since the
tubular fluid concentrations
change little relative to the
inulin concentration, all three
ions must be reabsorbed. The
small rise in the tubular fluid
chloride concentration over
the bicarbonate concentration
indicate that NaHCO3
absorption is preferred over NaCl absorption. However, since the filtered chloride concentration
(105 mM) is much greater than the bicarbonate concentration (25 mM), NaCl reabsorption is
dominate.

Reabsorption of Substances from the tubule: The barriers to be crossed.

To be reabsorbed (to move from the filtrate to the plasma), a substance must cross five distinct barriers:
1. The luminal cell membrane
2. The cytosol
3. The basolateral cell membrane
4. The interstitial fluid
5. The capillary wall

Mechanism of solute and water transport along the proximal tubule:

Since NaCl reabsorption
greatly exceeds NaHCO3 reabsorption in the proximal tubule, the mechanism of NaCl transport and
its coupling to H2O transport will be emphasized.

Isosmotic Fluid Reabsorption: definition

Coupling of H2O reabsorption to NaCl reabsorption.

Isosmotic Fluid Reabsorption: mechanism

Na+ enters the cell passively (dashed arrow) and then is actively transported into the intercellular space (dark, solid arrow). Cl- and H2O follow the movement of Na+ down passive electrical and osmotic gradients. The NaCl and water that enter the intercellular space can either move into the capillary and be returned to the systemic circulation or leak back into the lumen across the tight junction.

Isosmotic Fluid Reabsorption: Uptake into peritubular capillaries and the role of Starling's Forces

The Starling forces are responsible for peritubular capillary uptake of fluid.
Interstial fluid oncotic pressure, πif
Plasma oncotic pressure in the peritubular capillaries, πptc
Interstial fluid hydrostatic pressure, Pif
Hydrostatic pressure in the peritubular capillaries, Pptc
Capillary uptake = Kf[(πptc + Pif) - (πif + Pptc)]

Factors affecting the net rate of fluid reabsorption in the proximal tubule:

1. Proximal tubule active Na transport
2. Hemodynamic forces
3. Backflux through the tight junction

Proximal tubule active Na transport

Regulation of the Na pump activity influences the net rate of solute reabsorption and
hence, the net rate of fluid reabsorption

Hemodynamic forces

Regulation of hemodynamic factors in the peritubular capillaries controls the rate of
fluid uptake at the peritubular capillaries. This in turn controls the rate of net fluid
reabsorption by the epithelium.

Backflux through the tight junction

Regulation of the tight junction solute permeability influences the rate of solute back
flux through the tight junction, thereby directly influencing net solute reabsorption
and net fluid reabsorption

Glomerulotubular balance:

The phenomenon in which a tubular segment reabsorbs a relatively constant fraction of the fluid filtered at the glomerulus. There is a balance between tubular function (reabsorption) and glomerular function (filtration), hence the term glomerulotubular balance. This is depicted in the figure for the proximal tubule. Since factional Na+ and water reabsorption remains constant, absolute proximal reabsorption in a nephron is directly proportional to the single nephron filtration rate (SNGR). A similar relationship between absolute Na+ reabsorption and the amount of Na+ delivered to the segment is present in the loops of Henle and the distal tubule.

Reabsorption/secretion of inorganic ions by the proximal tubule: Bicarbonate reabsorption

Greater than 90% of the filtered load is reabsorbed in the proximal tubule. No evidence of a true Tm.

Reabsorption/secretion of inorganic ions by the proximal tubule: Potassium reabsorption

Seventy to 80% of the filtered load is reabsorbed in the proximal tubule. Regulation if K excretion is primarily a consequence of regulation of K secretion by the distal tubule and collecting duct—reabsorption of K by the proximal tubule is relatively constant.

Reabsorption/secretion of inorganic ions by the proximal tubule: Ca, Mg, and PO4 reabsorption

Partially reabsorbed in the proximal tubule, reabsorption characterized by a Tm.

Reabsorption of organic solutes:

secondary active transport system coupled to sodium entry at the luminal (apical) cell membrane (Tm systems).

Ex: Glucose and other sugars
Amino acids

Reabsorption of organic solutes: Protein reabsorption

Proteins are reabsorbed in the proximal tubule. Reabsorption occurs via an endocytic
mechanism which can be characterized by a Tm and RPT

Reabsorption of organic solutes: Urea reabsorption

passive transport;
As fluid is reabsorbed from
the proximal tubule, the concentration of urea in the luminal fluid will increase. This creates
a concentration gradient for urea which favors the passive diffusion of urea out of the tubule
lumen into the peritubular capillaries (passive reabsorption of urea). As a consequence of
this passive reabsorption, if fluid reabsorption in the proximal tubule is reduced, resulting in
an increase in urine flow, the concentration of urea in tubular fluid will be reduced. Hence,
the gradient for passive reabsorption will be decreased, bringing about a reduction in urea
reabsorption. Further, as urea reabsorption is reduced the rate of urea excretion will increase
proportionately.

Secretion of weak organic acids and bases:

1. Organic anion (acid) secretory system
Ex: Urate, PAH, penicillin, etc.
2. Organic cation (base) secretory system
Ex: Choline, quanidine, etc.

The proximal tubule end-product:

Percent of filtered load remaining at the end of the proximal tubule:

30-35% Water
30-35% NaCl
30% K
50% Urea
10% Bicarbonate
0% (trace only) Glucose, Amino Acids

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