PROXIMAL TUBULE FUNCTION
- Magnitude of Proximal Tubule Reabsorption
Since PNa = 145 mEq/L and GFR = 180 L/day, then 26100 mEq Na/day (equivalent to
Na in 1.566 kilogram salt) are filtered. Only 300 mEq Na/day are excreted in the urine.
Thus, about 99% is reabsorbed by the kidneys.
Most of the Na reabsorption takes place in the proximal tubule. The (TF/P)inulin
= 3 by the end of the proximal convoluted tubules(PCT). This indicates that
only 1/3 of the filtered water remains by the end of the PCT and two thirds have been
reabsorbed. The Na concentration in fluid sampled at the end of the PCT equals that in
plasma, (TF/P)Na =1. So, 2/3 of the filtered Na must also have been reabsorbed
along the PCT.
The osmolarity of the fluid along the PCT remains nearly equal to that in plasma (TF/P)osm=1.
So 2/3 of all filtered solutes are reabsorbed along with 2/3 of the filtered water along
the PCT. This is called isoosmotic reabsorption.
- Transport in the S1 Proximal Tubule Segment
Mechanisms: Luminal Na entry into S1 PCT cells via Na/H exchange (25% of the amount
reabsorbed), and via cotransport with glucose (5%) and amino acids (2%) and carboxylic
acids (1%), for a total of 33% of S1 Na reabsorption. The rest of the Na (66%) is
reabsorbed passively by solvent drag through the paracellular pathway. Of the Na that
enters the S1 PCT cells, about 3/4 is transported from the PCT cells into the interstitial
space by the Na-K ATPase at the basolateral side and the rest is extruded via basolateral
S1 is poorly permeable to Cl and urea, which rise in concentration along S1, compensating
in part for the decrease in concentrations of HCO3, glucose, amino and
carboxylic acids, phosphate and sulfate.
Water reabsorption along S1 is due to a small (4 mOsm/L) osmotic gradient
(lumen hypo-osmotic) due to preferential reabsorption of NaHCO3, Na with
glucose, amino and carboxylic acids and an extremely high permeability to water,
due to abundance of aquaporin water channels in PCT cell membranes.
When delivery of poorly reabsorbed solutes to the PCT increases (such as glucose in
diabetes mellitus, HCO3 when carbonic anhydrase is inhibited, or excess
filtered saline), osmotic water reabsorption and paracellular passive Na reabsorption by
solvent drag decrease and an osmotic diuresis may develop in which up to 66% of
filtered Na and water (66 ml/min) may be excreted as slightly hyperosmotic urine.
- Transport in the S2-S3 Proximal Tubule Segments
Along the S2 and S3 segments, the major transport process is the reabsorption of NaCl
through parallel Cl-/formate- and Na+/H+
exchanges at the luminal cell membrane.
Water reabsorption along S2 and S3 is driven by a small (4 mOsm/L) effective
osmotic radient generated by the lower osmotic effect of intraluminal Cl-
(reflection coeff. = 0.8), compared to peritubular HCO3-, glucose,
and amino acids (reflection coeff .= 1), in spite of similar intra- and peritubular total
osmolarities. The water permeability in these segments is also very high.
- Proximal Tubule Transport Regulation|
Regulation of Na+ and water reabsorption along the proximal tubule is by glomerular-
tubular (GT) balance: tubular reabsorption changes in proportion to the filtered load;
percent or fractional reabsorption remains constant. GT balance is due to intratubular and
Intratubular factors: At the high tubule flow rate associated with high GFR, the
decrease in the luminal concentrations of HCO3, glucose, and amino acids along
the PCT are less marked than at normal GFR. Thus, the more distal cells in S2 and S3 are
exposed to higher concentrations of these solutes when GFR is higher. High concentrations
promote the reabsorption of these solutes, coupled with Na which, in turn, increases the
osmotic reabsorption of water.
Peritubular factors: When GFR increases due to a rise in efferent resistance there
is an increase in peritubular capillary oncotic pressure (Ponc) and a decrease
in peritubular capillary hydrostatic pressure (Phydro), both of which reduce
interstitial fluid pressure and promote fluid and Na reabsorption proportionally to the
increase in GFR. (Note: oncotic pressure is the osmotic pressure developed by plasma
When mean arterial pressure (MAP), afferent resistance or oncotic pressure (Ponc)
change, there are adjustments of GT balance that lead to changes in fractional
reabsorption of Na and water along the PCT. Decrease in MAP, increase of afferent
arteriole resistance, or increase of peritubular capillary Ponc (common in
dehydration and volume depletion) lead to increases in proximal fractional
reabsorption of Na and water by reducing peritubular Phydro and/or interstitial
fluid pressure. The reverse occurs when MAP increases, afferent resistance decreases ,or
peritubular capillary Ponc decreases (common in overhydration or volume
Other factors: In addition to intrratubular factors and peritubular
Starling forces (physical factors), proximal tubule Na transport is also regulated by
hormones, such as AII and catecholamines, which will be discussed later.
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