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What is the principal determinant of ECF volume?

Sodium Concentration, [Na+]


How is [Na+], and hence plasma volume, principally regulated?

By renal excretion


What is the functional unit for renal excretion?

The nephron


What is the site of the ultrafiltration of blood?

The glomerulus


What are the characteristics of the ultrafiltrate produced at the glomerulus?

It is cell-free and protein-free, with an electrolyte profile resembling plasma


What proportion of fluid filtered at the glomerulus is reabsorbed by the tubules?

Over 99% of filtered fluid is recovered by the renal tubules


What is the main mechanism of fluid reabsorption in the renal tubules?

Fluid reabsorption is mainly forced by Na+ reabsorption


What is the glomerular filtration rate (GFR) of the average adult?

The average adult filters 125ml/min, equivalent to 180L/day


What are the five functional parts of the renal tubule, following the glomerulus?

  • Proximal convoluted tubule
  • Loop of Henle
  • Early distal convoluted tubule
  • Late distal tubule
  • Collecting duct

Functionally, the late distal tubule and collecting duct are very similar in their actions


What proportion of sodium is reabsorbed in the proximal tubule?

Some 65% of filtered Na+ is reabsorbed in the proximal convoluted tubule


Which pump exists in high density on the basolateral membrane of the proximal tubule, and what exchange does it make?

The Na,K-ATPase pump, expelling 3 Na+ ions into the blood in exchange for 2 K+ ions entering the cell


How does the sodium extruded by the basolateral membrane of the proximal tubule enter the cells?

Numerous apical membrane cotransporters, driven by the low intracellular [Na+], in turn forced by the Na, K-ATPase pump.


What substances do the apical membrane cotransporters in the proximal tubule reabsorb from the urine along with sodium?

Many, including:

  • glucose
  • amino acids
  • phosphate



What is the main apical membrane countertransport responsible for sodium reabsorption in the proximal tubule?

The main countertransport is the sodium-hydrogen exchanger (NHE-3)


Which enzyme creates the hydrogen ions required for the sodium-hydrogen exchanger (NHE-3)?

Carbonic anhydrase


Which reaction does carbonic anhydrase catalyse?

CO2 + H2O ⇒ H2CO3 ⇒ HCO3- + H+


Which other pathway accounts for a large proportion of the transepithelial flux of sodium, water and other dissolved solutes in the proximal tubule?

The gaps between cells, known as the 'shunt' pathway. This water follows the sodium concentration as the Na, K - ATPase forces flow of sodium into the intravascular compartment.


What is the overall fluid and electrolyte profile absorbed in the proximal convoluted tubule compared to plasma?

The proximal tubule reabsorbs largely isotonic fluid as compared to plasma, with similar water and sodium absorbed.


What forces water absorption in the proximal tubule?

The flow of water follows the sodium from urine to blood, as forced by the Na, K - ATPase


What are the two routes of water absorption in the proximal tubule?

The two routes are:

  1. Shunt transfer between cells
  2. Transfer through cells with aquaporin-1 (AQP-1) water channels


What proportion of sodium is reabsorbed in the loop of Henle?



How much water is reabsorbed in the loop of Henle?

No water is reabsorbed in the loop of Henle as it is impermeable to water


What is the principle force for sodium reabsoprtion in the loop of Henle?

Again, as in the proximal tubule, the main force is the Na, K ATP-ase on the basolateral membrane


Through what mechanism does the Na+ enter the cell through the apical membrane in the loop of Henle?

Sodium enters the cell via the K+, Na+,2Cl- triple cotransporter (NKCC2), which allows electroneutral entry of these ions into the cell


What happens to some of the K+ that enters the cell through the triple cotransporter and the Na, K ATPase in the loop of Henle?

The ROMK specific potassium channel in the apical membrane allows flow of potassium back into the luminal fluid. This allows a continuuing supply of K+ for the triple cotransporter


What electrical gradient exists in the lumen relative to the interstitium in the loop of Henle?

A small positive electrical gradient


What effect does this electrical gradient in the loop of Henle have?

This forces cations to be absorbed between cells in the shunt pathway, allowing for reabsorption of:

  • Na+
  • K+
  • Ca2+
  • Mg2+


What proportion of Na+ is reabsorbed from the early distal tubule?



What transporter drives the reabsorptive activity in the early distal tubule?

Again, the reabsorptive activity is driven by the Na, K-ATPase in the basolateral membrane, extruding 3 Na+ ions in return for taking up 2 K+ ions from the capillary


What is the chief route of Na+ entry into cells in the early distal tubule?

The sodium-choride cotransporter (NCCT) in the apical membrane, which allows for transport of one Na+ ion and one Cl- ion into the cell from the luminal fluid