The nephron, functional unit of the kidney, has three essential functions: glomerular filtration, tubular reabsorption and tubular secretion.
The normal glomerular filter is permeable to all the molecules whose molecular weight is lower than 68 000. The glomerular filtrate thus contains all the components of the plasma with a molecular weight lower than 68 000. The filtration is a passive phenomenon which depends on the concentration of the components on both sides of the filter and on blood flow rate. The volume filtered by the kidneys is 125 to 130 ml/minute, i.e. 180 L/24 h whereas the urinary elimination is approximately 1 ml/minute i.e. 1.5 L per 24 h.
Tubular reabsorption and secretion
Many structures present at apical and basal poles of the cells of the tubule are implicated in the transcellular transfers of ions among which one can quote:
- Exchangers: Na+/H+, Na+/HCO3-, Cl-/HCO3-
- Na+/HCO3-, present in particular at the basolateral pole of the cells of the proximal tubule
- Na+/substrate, the substrate being glucose, phosphate, lactate or an amino acid…
- Na+/K+-2Cl-, present in the ascending limb of Henle's loop
- Na+/Cl, present in the initial part of the distal tubule
- Na+/K+-ATPase pump, which uses the energy coming from the hydrolysis of ATP to ensure the egress out of the cell of three Na+ ions and the influx of two K+ ions, thus creating an electrochemical gradient. It is located at the basal pole of the epithelial cell.
In parallel passive transfer by paracellular route exists.
The reabsorption is done at several levels of the tubule.
- At the level of the proximal tubule, the longest part of the tubule having a great area of exchange, there is an active reabsorption of sodium present at high concentration, (approximately 65% of sodium filtered is reabsorbed there), of bicarbonate, sulfate, glucose, various acids and amino acids. The implicated mechanisms are, in particular, the Na+ /substrate cotransport and the exchange Na+/H+. Potassium is also reabsorbed but it is present at a concentration much lower than sodium.
This active reabsorption induces a passive reabsorption of water.
- At the level of Henle's loop,
- there is passive reabsorption of water from the descending limb
- there is active reabsorption of sodium, potassium and chloride by the cotransport Na+/ K+-2Cl- from the ascending limb, broad Henle's loop which is not permeable to water and is called segment of dilution. Approximately 25% of filtered sodium is reabsorbed at this level.
- At the level of the distal tubule,
- in the initial part, there is reabsorption of sodium by Na+ /Cl cotransport, nearly 10% of sodium is reabsorbed there;
- in the second part, there is reabsorption of sodium, which is induced by aldosterone.
- At the level of the collecting duct, there is a passive reabsorption of water, but only in the presence of the antidiuretic hormone which opens the pores of aquaporins allowing the reabsorption. There are also exchanges between sodium and potassium.
- At the level of the proximal tubule, there is secretion of H+ ions.
There is also secretion of many drugs - either with acid function: para-aminohippuric acid, thiazide diuretics, penicillin, indometacine, salicylic acid – or with basic function: histamine, thiamine, choline, quinine, morphine, amiloride.
- At the level of Henle's loop, there is no secretion.
- At the level of the distal tubule, there is secretion of H+ ions, ammonia and potassium. The urine of Henle's loop hardly contains potassium, the final urine contains some because it is secreted at the level of the distal tract.
There is competition between K+ and H+ for secretion into the lumen of the tubule in exchange of sodium: in case of potassium overload by oral administration of potassium chloride, potassium elimination increases while H+ elimination decreases with a consequent plasma acidosis and alkalization of urine. The inverse phenomenon is observed in case of potassium deficiency.
The following diagram indicates the point of impact of the various diuretics.
Simplified diagram of the nephron with the sites of action
of the three principal groups of diuretics: loop diuretics,
thiazide diuretics, potassium-sparing diuretics.
Sodium urinary elimination is low during the day in an upright subject and higher during the night in a lying subject. On the contrary the urinary potassium elimination is high during the day and low during the night.