Question 4

Describe the mechanisms by which water and electrolytes are reabsorbed across the renal tubules.

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College Answer

The intent of the question was to have the candidate describe in the context of a 
classification the mechanisms by which water and electrolytes may cross a cell membrane 
and use the renal tubule to provide an example of each mechanism. 
It was expected the answer would talk about transport “mechanisms” across membranes. 
These would include processes such as reabsorption, diffusion, facilitated diffusion, primary 
and secondary active transport, endocytosis, osmosis and solvent drag. Many candidates 
used colloquial and vague language to describe precise concepts.
Some candidates structured their answer as an outline of the principal mechanisms at each 
segment of the tubule. Thus there was repetitive reference to mechanisms without a 
description as requested in the question. This approach also resulted in some candidates 
omitting some mechanisms altogether.


Some might say that if "intent of the question was to have the candidate describe in the context of a classification the mechanisms by which water and electrolytes may cross a cell membrane", then perhaps the question itself should be worded, "Describe in the context of a classification the mechanisms by which water and electrolytes may cross a cell membrane; use the renal tubule as an example of each mechanism". This infuriatingly poor assessment design has led to 67% of the candidates failing this question purely because they read the question carefully and tried to answer it as it was phrased. 

So... What did they want? Perhaps something like this:

  • Diffusion:
    • Passive ("simple") diffusion: occurs along a concentration gradient directly through the lipid bilayer. Example: Water in the thin limb.
    • Facilitated diffusion: occurs along a concentration gradient, but requires a protein channel as a conduit. Example: Water in the collecting duct, via aquaporins
    • Ion channels:  selective conduit proteins,  which only allow the passage of specific ions. Example: sodium transport by apical sodium channels in the proximal tubule
  • Active transport:
    • Primary active transport: mediated by a "pump" protein which uses chemical energy stored in ATP to facilitate the transport of molecules (usually against their concentration gradient). Example: sodium and potassium transport by Na+/K+ ATPase in the proximal tubule.
    • Secondary active transport: mediated by an exchaner or co-transporter which facilitates the movement of molecules using the energy of a concentration gradient set up by another (primary) ATP-powered transport process. Example: sodium and glucose co-transport in the proximal tubule.
  • Vesicle transport
    • Endocytosis: where the transport of substances into the cell occurs by formation membrane-bounded vesicles containing the substance. Example: uptake of insulin in the proximal tubule
    • Exocytosis: the opposite of endocytosis, where vesicles transport molecules to the cell surface and empty their contents into the extracellular fluid.  Example: secretion of urodilatin, a natriuretic peptide, out of distal convoluted tubule cells.

So, they asked "describe the mechanisms by which water and electrolytes are reabsorbed across the renal tubules", where they actually mean was "describe the mechanism by which molecules can cross membranes, using the tubule as an example". Most people seem to have interpreted this SAQ quite literally, and described the handling of water and solutes in the different segments of the nephron, which turned out to be a disastrous move. Only 33% of them passed. The following answer therefore addresses the remaining 67%, and transports them to a parallel universe where CICM exam answers have some direct relationship with the phrasing of CICM exam questions.

Water Handling in the Nephron
Segment What happens to water Regulatory mechanisms
  • Filtered freely in the glomerulus
  • Rate of filtration is directly proportional to glomerular blood flow.

Main mechanism is to influence glomerular blood flow:

  • Tubuloglomerular feedback
  • Renal blood flow autoregulation
  • Sympathetic nervous system
  • Vasoactive substances which affect the afferent and efferent arterioles
Proximal convoluted tubule
  • Reabsorbed through the highly permeable tubule wall
  • Absorption is driven by sodium gradient which is generated by Na/K ATPase
  • Glomerular filtration rate
  • Natriuretic peptides
Descending thin limb
  • Reabsorbed through the highly permeable tubule wall
  • Absorption is driven by the osmotic pull of the increasingly hypertonic medullary interstitium
  • Not under any direct regulatory control
Ascending thin and thick limbs
  • Diluted by the removal of solutes
  • Natriuretic peptides
Distal convoluted tubule
  • Diluted by the removal of solutes
  • Aldosterone (increases solute removal and therefore tubular fluid dilution)
Connecting tubule and collecting duct
  • Rebasorbed through aquaporin channels
  • Driven mainly by the hypertonic medullary interstitium
  • Vasopressin (increases water reabsorption)
  • Aldosterone (increases osmotic gradient for water reabsorption)


Wilson, David B. "Cellular transport mechanisms." Annual review of biochemistry 47.1 (1978): 933-965.

Yang, Nicole J., and Marlon J. Hinner. "Getting across the cell membrane: an overview for small molecules, peptides, and proteins." Site-Specific Protein Labeling. Humana Press, New York, NY, 2015. 29-53.

Stein, Wilfred. Transport and diffusion across cell membranesElsevier, 2012.

Cussler, E. L., Rutherford Aris, and Abhoyjit Bhown. "On the limits of facilitated diffusion." Journal of membrane science43.2-3 (1989): 149-164.

Wu, Ling-Gang, et al. "Exocytosis and endocytosis: modes, functions, and coupling mechanisms." Annual review of physiology 76 (2014): 301-331.