Proximal tubular function

[box type=”download”]  Appreciation of the principal agents reabsorbed at this site  Understanding of the particular dynamics of sodium and glucose in this region[/box]

The proximal tubule

Most glucose, amino acids, phosphate and bicarbonate is reabsorbed in the proximal tubule, together with
60–70% of Na+, K+, Ca2+, urea and water.

Sodium.

The filtrate concentration of Na+ is ∼140 mmol/L (= plasma Na+ concentration), but is much lower in the cytosol of epithelial cells (∼10–20 mmol/L), which is also negatively charged.
The electrochemical gradient therefore drives Na+ from the filtrate into the cells. (Also the driving force for the secondary transport of other substances)
About 80% of Na+ entering proximal tubular cells exchanges for H+ (Na+–H+ antiporter).
The secretion of H+ in the proximal tubule plays a critical role in HCO3− reabsorption.
Na+ is removed from tubular cells by Na+ pumps on the basolateral membrane, thus transporting Na+ into the interstitial fluid.
However, only ∼20% of transported Na+ diffuses into the capillaries, as there is significant backflux into the tubule via paracellular pathways.


Water.

As Na+ and HCO3 − are transported from the tubule into the peritubular interstitial fluid, the osmolality of the latter increases, and this osmotic pressure causes reabsorption of water.
The reabsorption of water increases tubular concentrations of Cl−, K+, Ca2+ and urea, which therefore diffuse down their concentration gradients into the peritubular space, largely via paracellular pathways.
The final two-thirds of the proximal tubule has increased permeability to Cl−, facilitating Cl− reabsorption.
This makes the lumen more positive, enhancing the reabsorption of cations.
As the reabsorption of Na+, Cl−, K+, Ca2+ and urea in the proximal tubule is closely coupled to the reabsorption of water, their concentrations (and the total osmolality) are similar in the fluid leaving the proximal tubule to those in the filtrate and plasma, although their total quantity and the fluid volume are decreased by ∼70%.


Glucose.

Glucose is reabsorbed by cotransport with Na+ across the apical membrane of epithelial cells, and then diffuses out of the cells into the peritubular interstitium.
The Tm for glucose is ∼380 mg/min (∼21 mmol/min), and the renal threshold is ∼11 mmol/L.
The appearance of glucose in the urine reflects hyperglycaemia (high plasma glucose), a sign of diabetes mellitus.

Amino acids

reabsorbed by several Na+-linked symporters, specific for acidic, basic and neutral amino acids.

Phosphate.

Phosphate is cotransported with Na+ across the epithelial apical membrane.
Its Tm is close to the filtered load, and so an increase in plasma concentration leads to excretion.
Phosphate reabsorption is decreased by PTH.

Organic acids and bases.

These include metabolites (e.g. bile salts, urate, oxalate) and drugs (e.g. PAH, penicillins, aspirin) and are secreted.
Organic acids are transported from the peritubular fluid into tubular cells by cotransport with Na+, and diffuse into the tubule in exchange for anions (e.g. Cl−, HCO3−).
Organic bases are actively extruded from the apical membrane in exchange for Na+ or H+.

Proteins/peptides.

The tiny amount of protein that does escape through the glomerular filter and small peptide hormones (e.g. insulin, growth hormone) are reabsorbed by endocytosis and destroyed.

Lesson tags: amino acids, glucose, organic acids, organic bases, phosphate, proximal tubule, sodium
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